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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Abstract

Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.

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[1]
WHO Epilepsy. Available from: https://www.who.int/news-room/fact-sheets/detail/epilepsy
[2]
Thijs, R.D.; Surges, R.; O’Brien, T.J.; Sander, J.W. Epilepsy in adults. Lancet, 2019, 393(10172), 689-701.
[http://dx.doi.org/10.1016/S0140-6736(18)32596-0] [PMID: 30686584]
[3]
Fisher, R.S.; Cross, J.H.; French, J.A.; Higurashi, N.; Hirsch, E.; Jansen, F.E.; Lagae, L.; Moshé, S.L.; Peltola, J.; Roulet Perez, E.; Scheffer, I.E.; Zuberi, S.M. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia, 2017, 58(4), 522-530.
[http://dx.doi.org/10.1111/epi.13670] [PMID: 28276060]
[4]
Fisher, R.S.; Cross, J.H.; D’Souza, C.; French, J.A.; Haut, S.R.; Higurashi, N.; Hirsch, E.; Jansen, F.E.; Lagae, L.; Moshé, S.L.; Peltola, J.; Roulet Perez, E.; Scheffer, I.E.; Schulze-Bonhage, A.; Somerville, E.; Sperling, M.; Yacubian, E.M.; Zuberi, S.M. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia, 2017, 58(4), 531-542.
[http://dx.doi.org/10.1111/epi.13671] [PMID: 28276064]
[5]
Falco-Walter, J.J.; Scheffer, I.E.; Fisher, R.S. The new definition and classification of seizures and epilepsy, 2018, Vol. 139, 73-79.
[6]
Thomas, R.H.; Cunningham, M.O. Cannabis and epilepsy. Pract. Neurol., 2018, 18(6), 465-471. Available from: https://pn.bmj.com/content/18/6/465
[http://dx.doi.org/10.1136/practneurol-2018-002058] [PMID: 30337476]
[7]
Löscher, W.; Potschka, H.; Sisodiya, S.M.; Vezzani, A. Drug resistance in epilepsy: Clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol. Rev., 2020, 72(3), 606-638. Available from: https://pharmrev.aspetjournals.org/content/72/3/606
[http://dx.doi.org/10.1124/pr.120.019539] [PMID: 32540959]
[8]
Neelam, K.A.; Khatkar, A.; Sharma, K.K. Phenylpropanoids and its derivatives: biological activities and its role in food, pharmaceutical and cosmetic industries. Crit. Rev. Food Sci. Nutr., 2020, 60(16), 2655-2675. Available from: https://pubmed.ncbi.nlm.nih.gov/31456411/
[http://dx.doi.org/10.1080/10408398.2019.1653822] [PMID: 31456411]
[9]
Löscher, W. Single-target versus multi-target drugs versus combinations of drugs with multiple targets: Preclinical and clinical evidence for the treatment or prevention of epilepsy. Front. Pharmacol., 2021, 12, 730257.
[http://dx.doi.org/10.3389/fphar.2021.730257] [PMID: 34776956]
[10]
Kitchen, D.B.; Decornez, H.; Furr, J.R.; Bajorath, J. Docking and scoring in virtual screening for drug discovery: Methods and applications. 2004. Available from: https://www.nature.com/articles/nrd1549
[http://dx.doi.org/10.1038/nrd1549]
[11]
German, S.-M. Extrasynaptic GABA and glutamate receptors in epilepsy. CNS Neurol. Disord. Drug Targets, 2008, 6(4), 288-300.
[12]
Sarlo, G.L.; Holton, K.F. Brain concentrations of glutamate and GABA in human epilepsy: A review. Seizure, 2021, 91, 213-227.
[http://dx.doi.org/10.1016/j.seizure.2021.06.028] [PMID: 34233236]
[13]
Ghit, A.; Assal, D.; Al-shami, A.S.; Hussein, D.E.E. GABAA receptors : structure, function, pharmacology, and related disorders. J. Genet. Eng. Biotechnol., 2021, 19(1), 123.
[14]
Treiman, D.M. GABAergic mechanisms in epilepsy. Epilepsia, 2001, 42(s3)(Suppl. 3), 8-12.
[http://dx.doi.org/10.1046/j.1528-1157.2001.042suppl.3008.x] [PMID: 11520315]
[15]
Cossart, R.; Bernard, C.; Ben-Ari, Y. Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies. Trends Neurosci., 2005, 28(2), 108-115.
[http://dx.doi.org/10.1016/j.tins.2004.11.011] [PMID: 15667934]
[16]
Watanabe, M.; Maemura, K.; Kanbara, K.; Tamayama, T.; Hayasaki, H. GABA and GABA receptors in the central nervous system and other organs. Int. Rev. Cytol., 2002, 213, 1-47.
[http://dx.doi.org/10.1016/S0074-7696(02)13011-7] [PMID: 11837891]
[17]
Eibl, C.; Plested, A.J.R. AMPA receptors: Mechanisms of auxiliary protein action. Curr. Opin. Physiol., 2018, 2, 84-91.
[http://dx.doi.org/10.1016/j.cophys.2017.12.009]
[18]
Moldrich, R.X.; Beart, P.M.; Jane, D.E.; Chapman, A.G.; Meldrum, B.S. Anticonvulsant activity of 3,4-dicarboxyphenylglycines in DBA/2 mice. Neuropharmacology, 2001, 40(5), 732-735.
[http://dx.doi.org/10.1016/S0028-3908(01)00002-8] [PMID: 11311902]
[19]
Kwan, P.; Brodie, M.J. Epilepsy after the first drug fails: Substitution or add-on? Seizure, 2000, 9(7), 464-468.
[http://dx.doi.org/10.1053/seiz.2000.0442] [PMID: 11034869]
[20]
Kohl, B.; Dannhardt, G. The NMDA receptor complex: A promising target for novel antiepileptic strategies. Curr. Med. Chem., 2001, 8(11), 1275-1289.
[http://dx.doi.org/10.2174/0929867013372328] [PMID: 11562266]
[21]
Zhou, H.X.; Wollmuth, L.P. Advancing NMDA receptor physiology by Integrating multiple approaches. Trends Neurosci., 2017, 40(3), 129-137.
[http://dx.doi.org/10.1016/j.tins.2017.01.001] [PMID: 28187950]
[22]
Löscher, W.; Schmidt, D. New horizons in the development of antiepileptic drugs: Innovative strategies. Epilepsy Res., 2006, 69(3), 183-272.
[http://dx.doi.org/10.1016/j.eplepsyres.2006.03.014] [PMID: 16835945]
[23]
Löscher, W. New visions in the pharmacology of anticonvulsion. Eur. J. Pharmacol., 1998, 342(1), 1-13.
[http://dx.doi.org/10.1016/S0014-2999(97)01514-8] [PMID: 9544786]
[24]
Featherstone, D.E. Intercellular glutamate signaling in the nervous system and beyond. ACS Chem. Neurosci., 2010, 1(1), 4-12.
[http://dx.doi.org/10.1021/cn900006n] [PMID: 22778802]
[25]
Deuis, J.R.; Mueller, A.; Israel, M.R.; Vetter, I. The pharmacology of voltage-gated sodium channel activators. Neuropharmacology, 2017, 127, 87-108.
[http://dx.doi.org/10.1016/j.neuropharm.2017.04.014] [PMID: 28416444]
[26]
Ghovanloo, M-R.; Aimar, K.; Ghadiry-Tavi, R.; Yu, A.; Ruben, P.C. Physiology and pathophysiology of sodium channel inactivation. Curr. Top. Membr., 2016, 78, 479-509.
[http://dx.doi.org/10.1016/bs.ctm.2016.04.001] [PMID: 27586293]
[27]
Catterall, W.A. From ionic currents to molecular mechanisms: The structure and function of voltage-gated sodium channels. Neuron, 2000, 26(1), 13-25.
[http://dx.doi.org/10.1016/S0896-6273(00)81133-2] [PMID: 10798388]
[28]
Brodie, M.J. Sodium channel blockers in the treatment of epilepsy. CNS Drugs, 2017, 31(7), 527-534.
[http://dx.doi.org/10.1007/s40263-017-0441-0] [PMID: 28523600]
[29]
Catterall, W.A.; Few, A.P. Calcium channel regulation and presynaptic plasticity. Neuron, 2008, 59(6), 882-901.
[http://dx.doi.org/10.1016/j.neuron.2008.09.005] [PMID: 18817729]
[30]
Catterall, W.A. Voltage-gated calcium channels. Cold Spring Harb. Perspect. Biol., 2011, 3(8), a003947-a003947.
[http://dx.doi.org/10.1101/cshperspect.a003947] [PMID: 21746798]
[31]
Rajakulendran, S.; Hanna, M.G. The role of calcium channels in epilepsy. Cold Spring Harb. Perspect. Med., 2016, 6(1), a022723.
[http://dx.doi.org/10.1101/cshperspect.a022723] [PMID: 26729757]
[32]
Prakriya, M.; Lewis, R.S. Store-operated calcium channels. Physiol. Rev., 2015, 95(4), 1383-1436.
[http://dx.doi.org/10.1152/physrev.00020.2014] [PMID: 26400989]
[33]
Berridge, M.J.; Lipp, P.; Bootman, M.D. The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol., 2000, 1(1), 11-21.
[http://dx.doi.org/10.1038/35036035] [PMID: 11413485]
[34]
Steinlein, O.K. Calcium signaling and epilepsy. Cell Tissue Res., 2014, 357(2), 385-393.
[http://dx.doi.org/10.1007/s00441-014-1849-1] [PMID: 24723228]
[35]
Ozcan, M.; Ayar, A. Modulation of action potential and calcium signaling by levetiracetam in rat sensory neurons. J. Recept. Signal Transduct. Res., 2012, 32(3), 156-162.
[http://dx.doi.org/10.3109/10799893.2012.672993] [PMID: 22475033]
[36]
Takahashi, E.; Niimi, K.; Itakura, C. Levetiracetam-mediated emotional behavior in heterozygous rolling Nagoya CaV2.1 channel mutant mice. Pharmacol. Biochem. Behav., 2010, 96(3), 294-300.
[http://dx.doi.org/10.1016/j.pbb.2010.05.020] [PMID: 20570694]
[37]
Sun, J.; MacKinnon, R. Structural basis of human KCNQ1 modulation and gating. Cell, 2020, 180(2), 340-347.e9.
[http://dx.doi.org/10.1016/j.cell.2019.12.003] [PMID: 31883792]
[38]
Abbott, G.W.; Tai, K.K.; Neverisky, D.L.; Hansler, A.; Hu, Z.; Roepke, T.K.; Lerner, D.J.; Chen, Q.; Liu, L.; Zupan, B.; Toth, M.; Haynes, R.; Huang, X.; Demirbas, D.; Buccafusca, R.; Gross, S.S.; Kanda, V.A.; Berry, G.T. KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability. Sci. Signal., 2014, 7(315), ra22.
[http://dx.doi.org/10.1126/scisignal.2005025] [PMID: 24595108]
[39]
Jespersen, T.; Grunnet, M.; Olesen, S.P. The KCNQ1 potassium channel: from gene to physiological function. Physiology (Bethesda), 2005, 20(6), 408-416.
[http://dx.doi.org/10.1152/physiol.00031.2005] [PMID: 16287990]
[40]
Brown, D.A.; Passmore, G.M. Neural KCNQ (Kv7) channels. Br. J. Pharmacol., 2009, 156(8), 1185-1195.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00111.x] [PMID: 19298256]
[41]
Zaydman, M.A.; Cui, J. PIP2 regulation of KCNQ channels: biophysical and molecular mechanisms for lipid modulation of voltage-dependent gating. Front. Physiol., 2014, 5, 195.
[http://dx.doi.org/10.3389/fphys.2014.00195] [PMID: 24904429]
[42]
Zaydman, M.A.; Silva, J.R.; Delaloye, K.; Li, Y.; Liang, H.; Larsson, H.P.; Shi, J.; Cui, J. Kv7.1 ion channels require a lipid to couple voltage sensing to pore opening. Proc. Natl. Acad. Sci. USA, 2013, 110(32), 13180-13185.
[http://dx.doi.org/10.1073/pnas.1305167110] [PMID: 23861489]
[43]
Zimprich, F.; Ronen, G.M.; Stögmann, W.; Baumgartner, C.; Stögmann, E.; Rett, B.; Pappas, C.; Leppert, M.; Singh, N.; Anderson, V.E. Andreas Rett and benign familial neonatal convulsions revisited. Neurology, 2006, 67(5), 864-866.
[http://dx.doi.org/10.1212/01.wnl.0000234066.46806.90] [PMID: 16966552]
[44]
Gunthorpe, M.J.; Large, C.H.; Sankar, R. The mechanism of action of retigabine (ezogabine), a first‐in‐class K+ channel opener for the treatment of epilepsy. Epilepsia, 2012, 53(3), 412-424.
[http://dx.doi.org/10.1111/j.1528-1167.2011.03365.x] [PMID: 22220513]
[45]
Cherubini, E.; Conti, F. Generating diversity at GABAergic synapses. Trends Neurosci., 2001, 24(3), 155-162.
[http://dx.doi.org/10.1016/S0166-2236(00)01724-0] [PMID: 11182455]
[46]
Kinjo, A.; Koito, T.; Kawaguchi, S.; Inoue, K. Evolutionary History of the GABA Transporter (GAT) Group Revealed by Marine Invertebrate GAT-1. Moustafa A, editor. PLoS One, 2013, 8(12), e82410.
[47]
Zafar, S.; Jabeen, I. Structure, function, and modulation of γ-aminobutyric acid transporter 1 (GAT1) in neurological disorders: A pharmacoinformatic prospective. Front Chem., 2018, 6, 397.
[http://dx.doi.org/10.3389/fchem.2018.00397] [PMID: 30255012]
[48]
Scimemi, A. Structure, function, and plasticity of GABA transporters. Front. Cell. Neurosci., 2014, 8, 161.
[http://dx.doi.org/10.3389/fncel.2014.00161] [PMID: 24987330]
[49]
Liu, Q.R.; López-Corcuera, B.; Mandiyan, S.; Nelson, H.; Nelson, N. Molecular characterization of four pharmacologically distinct γ-aminobutyric acid transporters in mouse brain [corrected] J. Biol. Chem., 1993, 268(3), 2106-2112.
[http://dx.doi.org/10.1016/S0021-9258(18)53968-5]
[50]
Keynan, S.; Suh, Y.J.; Kanner, B.I.; Rudnick, G. Expression of a cloned. gamma.-aminobutyric acid transporter in mammalian cells. Biochemistry, 1992, 31(7), 1974-1979.
[http://dx.doi.org/10.1021/bi00122a011] [PMID: 1536839]
[51]
Minelli, A.; Brecha, N.C.; Karschin, C.; DeBiasi, S.; Conti, F. GAT-1, a high-affinity GABA plasma membrane transporter, is localized to neurons and astroglia in the cerebral cortex. J. Neurosci., 1995, 15(11), 7734-7746.
[http://dx.doi.org/10.1523/JNEUROSCI.15-11-07734.1995] [PMID: 7472524]
[52]
Conti, F.; Melone, M.; de Biasi, S.; Minelli, A.; Brecha, N.C.; Ducati, A. Neuronal and glial localization of GAT-1, a high-affinity? -aminobutyric acid plasma membrane transporter, in human cerebral cortex: With a note on its distribution in monkey cortex. J. Comp. Neurol., 1998, 396(1), 51-63.
[http://dx.doi.org/10.1002/(SICI)1096-9861(19980622)396:1<51:AID-CNE5>3.0.CO;2-H] [PMID: 9623887]
[53]
Braestrup, C.; Nielsen, E.B.; Sonnewald, U.; Knutsen, L.J.S.; Andersen, K.E.; Jansen, J.A.; Frederiksen, K.; Andersen, P.H.; Mortensen, A.; Suzdak, P.D. (R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain gamma-aminobutyric acid uptake carrier. J. Neurochem., 1990, 54(2), 639-647.
[http://dx.doi.org/10.1111/j.1471-4159.1990.tb01919.x] [PMID: 2299358]
[54]
Froestl, W. An historical perspective on GABAergic drugs. Future Med. Chem., 2011, 3(2), 163-175.
[http://dx.doi.org/10.4155/fmc.10.285] [PMID: 21428811]
[55]
Jasmin, L; Wu, M; Ohara, P. GABA puts a stop to pain. Curr Drug Target -CNS Neurol Disord., 2004, 3(6), 487-505.
[http://dx.doi.org/10.2174/1568007043336716]
[56]
Mostafa, S.; Wang, Y.; Zeng, W.; Jin, B. Floral scents and fruit aromas: Functions, compositions, biosynthesis, and regulation [internet]. Front. Plant Sci., 2022, 13. Available from: https://www.frontiersin.org/articles/10.3389/fpls.2022.860157
[57]
Naoumkina, M.A.; Zhao, Q.; Gallego-Giraldo, L.; Dai, X.; Zhao, P.X.; Dixon, R.A. Genome‐wide analysis of phenylpropanoid defence pathways. Mol. Plant Pathol., 2010, 11(6), 829-846.
[http://dx.doi.org/10.1111/j.1364-3703.2010.00648.x] [PMID: 21029326]
[58]
Tossi, V.; Amenta, M.; Lamattina, L.; Cassia, R. Retracted: Nitric oxide enhances plant ultraviolet‐B protection up‐regulating gene expression of the phenylpropanoid biosynthetic pathway. Plant Cell Environ., 2011, 34(6), 909-921.
[http://dx.doi.org/10.1111/j.1365-3040.2011.02289.x] [PMID: 21332509]
[59]
Dixon, R.A.; Paiva, N.L. Stress-induced phenylpropanoid metabolism. Plant Cell, 1995, 7(7), 1085-1097.
[http://dx.doi.org/10.2307/3870059] [PMID: 12242399]
[60]
Peled-Zehavi, H.; Oliva, M.; Xie, Q.; Tzin, V.; Oren-Shamir, M.; Aharoni, A.; Galili, G. Metabolic engineering of the phenylpropanoid and its primary, precursor pathway to enhance the flavor of fruits and the aroma of flowers. Bioengineering (Basel), 2015, 2(4), 204-212.
[http://dx.doi.org/10.3390/bioengineering2040204] [PMID: 28952478]
[61]
Liu, J.; Osbourn, A.; Ma, P. MYB transcription factors as regulators of phenylpropanoid metabolism in plants. Mol. Plant, 2015, 8(5), 689-708.
[http://dx.doi.org/10.1016/j.molp.2015.03.012] [PMID: 25840349]
[62]
Rehman, F.; Khan, F.A.; Badruddin, S.M.A. Role of phenolics in plant defense against insect herbivory. Chem. Phytopotentials Heal Energy Environ. Perspect, 2012, 309-313.
[http://dx.doi.org/10.1007/978-3-642-23394-4_65]
[63]
Singh, R.; Rastogi, S.; Dwivedi, U.N. Phenylpropanoid metabolism in ripening fruits. Compr. Rev. Food Sci. Food Saf., 2010, 9(4), 398-416.
[http://dx.doi.org/10.1111/j.1541-4337.2010.00116.x] [PMID: 33467837]
[64]
Xiao, X.; Li, J.; Lyu, J.; Hu, L.; Wu, Y.; Tang, Z.; Yu, J.; Calderón-Urrea, A. Grafting-enhanced tolerance of cucumber to toxic stress is associated with regulation of phenolic and other aromatic acids metabolism. PeerJ, 2022, 10, e13521.
[http://dx.doi.org/10.7717/peerj.13521] [PMID: 35669966]
[65]
Mora, J.; Pott, D.M.; Osorio, S.; Vallarino, J.G. Regulation of plant tannin synthesis in crop species [internet]. Front. Genet., 2022, 13. Available from: https://www.frontiersin.org/articles/10.3389/fgene.2022.870976
[66]
Kumar, M.; Dahuja, A.; Tiwari, S.; Punia, S.; Tak, Y.; Amarowicz, R.; Bhoite, A.G.; Singh, S.; Joshi, S.; Panesar, P.S.; Prakash Saini, R.; Pihlanto, A.; Tomar, M.; Sharifi-Rad, J.; Kaur, C. Recent trends in extraction of plant bioactives using green technologies: A review. Food Chem., 2021, 353, 129431. Available from: https://www.sciencedirect.com/science/article/pii/S0308814621004374
[http://dx.doi.org/10.1016/j.foodchem.2021.129431] [PMID: 33714109]
[67]
Singh, P.; Singh, A.; Choudhary, K.K. Revisiting the role of phenylpropanoids in plant defense against UV-B stress. Plant Stress, 2023, 7, 100143. Available from: https://www.sciencedirect.com/science/article/pii/S2667064X23000131 [Internet]
[http://dx.doi.org/10.1016/j.stress.2023.100143]
[68]
Cunha, F.V.M.; Coelho, A.G.; Azevedo, P.S da S.; da Silva, A.A.; Oliveira, F de A.; Nunes, L.C.C. Systematic review and technological prospection: ethyl ferulate, a phenylpropanoid with antioxidant and neuroprotective actions. Expert Opin. Ther. Pat., 2019, 29(2), 73-83.
[http://dx.doi.org/10.1080/13543776.2019.1568410]
[69]
Sultana, R. Ferulic acid ethyl ester as a potential therapy in neurodegenerative disorders. Biochim. Biophys. Acta Mol. Basis Dis., 2012, 1822(5), 748-752.
[http://dx.doi.org/10.1016/j.bbadis.2011.10.015] [PMID: 22064438]
[70]
Kikuzaki, H.; Hisamoto, M.; Hirose, K.; Akiyama, K.; Taniguchi, H. Antioxidant properties of ferulic acid and its related compounds. J. Agric. Food Chem., 2002, 50(7), 2161-2168.
[http://dx.doi.org/10.1021/jf011348w] [PMID: 11902973]
[71]
Carvalho, A.A.; Andrade, L.N.; de Sousa, É.B.V.; de Sousa, D.P. Antitumor phenylpropanoids found in essential oils. BioMed Res. Int., 2015, 2015, 392674.
[http://dx.doi.org/10.1155/2015/392674]
[72]
Abreu, L.S.; do Nascimento, Y.M.; do Espirito-Santo, R.F.; Meira, C.S.; Santos, I.P.; Brandão, R.B.; Souto, A.L.; Guedes, M.L.S.; Soares, M.B.P.; Villarreal, C.F.; da Silva, M.S.; Velozo, E.S.; Tavares, J.F. Phenylpropanoids from Croton velutinus with cytotoxic, trypanocidal and anti-inflammatory activities. Fitoterapia, 2020, 145, 104632.
[http://dx.doi.org/10.1016/j.fitote.2020.104632] [PMID: 32446709]
[73]
Ekinci Akdemir, F.; Albayrak, M.; Çalik, M.; Bayir, Y.; Gülçin, İ. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines, 2017, 5(4), 18.
[http://dx.doi.org/10.3390/biomedicines5020018] [PMID: 28536361]
[74]
Abdel-Moneim, A.; El-Twab, S.M.A.; Yousef, A.I.; Reheim, E.S.A.; Ashour, M.B. Modulation of hyperglycemia and dyslipidemia in experimental type 2 diabetes by gallic acid and p-coumaric acid: The role of adipocytokines and PPARγ. Biomed. Pharmacother., 2018, 105, 1091-1097.
[http://dx.doi.org/10.1016/j.biopha.2018.06.096] [PMID: 30021345]
[75]
Panda, P.; Appalashetti, M.; Judeh, Z.M. Phenylpropanoid sucrose esters: Plant-derived natural products as potential leads for new therapeutics. Curr. Med. Chem., 2011, 18(21), 3234-3251.
[http://dx.doi.org/10.2174/092986711796391589] [PMID: 21671860]
[76]
Roy, S.K.; Pahwa, S.; Nandanwar, H.; Jachak, S.M. Phenylpropanoids of Alpinia galanga as efflux pump inhibitors in Mycobacterium smegmatis mc2 155. Fitoterapia, 2012, 83(7), 1248-1255.
[http://dx.doi.org/10.1016/j.fitote.2012.06.008] [PMID: 22735598]
[77]
Phitak, T.; Choocheep, K.; Pothacharoen, P.; Pompimon, W.; Premanode, B.; Kongtawelert, P. The effects of p-hydroxy-cinnamaldehyde from Alpinia galanga extracts on human chondrocytes. Phytochemistry, 2009, 70(2), 237-243.
[http://dx.doi.org/10.1016/j.phytochem.2008.11.010] [PMID: 19118849]
[78]
Marchiosi, R.; dos Santos, W.D.; Constantin, R.P.; de Lima, R.B.; Soares, A.R.; Finger-Teixeira, A.; Mota, T.R.; de Oliveira, D.M.; Foletto-Felipe, M.P.; Abrahão, J.; Ferrarese-Filho, O. Biosynthesis and metabolic actions of simple phenolic acids in plants. Phytochem. Rev., 2020, 19(4), 865-906.
[http://dx.doi.org/10.1007/s11101-020-09689-2]
[79]
Widhalm, J.R.; Dudareva, N. A familiar ring to it: Biosynthesis of plant benzoic acids. Mol. Plant, 2015, 8(1), 83-97.
[http://dx.doi.org/10.1016/j.molp.2014.12.001] [PMID: 25578274]
[80]
Charanya, C.; Sampathkrishnan, S.; Balamurugan, N. Molecular docking, vibrational spectroscopic analysis, non-linear optical properties and DFT Calculation of 2-[(2,3-Dimethylphenyl)Amino] Benzoic Acid. 2019. Available from: https://www.tandfonline.com/doi/abs/10.1080/10406638.2019.1700138
[81]
Natchimuthu, V.; Bandaru, S.; Nayarisseri, A.; Ravi, S. Design, synthesis and computational evaluation of a novel intermediate salt of N-cyclohexyl-N-(cyclohexylcarbamoyl)-4-(trifluoromethyl) benzamide as potential potassium channel blocker in epileptic paroxysmal seizures. Comput. Biol. Chem., 2016, 64, 64-73.
[http://dx.doi.org/10.1016/j.compbiolchem.2016.05.003] [PMID: 27266485]
[82]
Kumar, A.; Kumar, A. Design and synthesis of anti-convulsant and anti-bacterial activity of new hydrazone derivatives. Available from: https://biointerfaceresearch.com/wp-content/uploads/2020/02/20695837102229236.pdf
[http://dx.doi.org/10.33263/BRIAC102.229236]
[83]
de Souza, L.G.; Rennó, M.N.; Figueroa-Villar, J.D. Coumarins as cholinesterase inhibitors: A review. Chem. Biol. Interact., 2016, 254, 11-23.
[http://dx.doi.org/10.1016/j.cbi.2016.05.001] [PMID: 27174134]
[84]
Franco, D.P.; Pereira, T.M.; Vitorio, F.; Nadur, N.F.; Lacerda, R.B.; Kümmerle, A.E. A importância das cumarinas para a química medicinal e o desenvolvimento de compostos bioativos nos últimos anos. Quim, 2021, 44(2), 180-197.
[85]
Kostova, I. Synthetic and natural coumarins as antioxidants. Mini Rev. Med. Chem., 2006, 6(4), 365-374.
[http://dx.doi.org/10.2174/138955706776361457] [PMID: 16613573]
[86]
Mohammadi-Khanaposhtani, M.; Ahangar, N.; Sobhani, S.; Masihi, P.H.; Shakiba, A.; Saeedi, M.; Akbarzadeh, T. Design, synthesis, in vivo, and in silico evaluation of new coumarin-1,2,4-oxadiazole hybrids as anticonvulsant agents. Bioorg. Chem., 2019, 89, 102989.
[http://dx.doi.org/10.1016/j.bioorg.2019.102989] [PMID: 31158578]
[87]
Sepehri, N.; Mohammadi-Khanaposhtani, M.; Asemanipoor, N.; Hosseini, S.; Biglar, M.; Larijani, B.; Mahdavi, M.; Hamedifar, H.; Taslimi, P.; Sadeghian, N.; Gulcin, I. Synthesis, characterization, molecular docking, and biological activities of coumarin-1,2,3‐triazole‐acetamide hybrid derivatives. Arch. Pharm. (Weinheim), 2020, 353(10), 2000109.
[http://dx.doi.org/10.1002/ardp.202000109] [PMID: 32643792]
[88]
Abd-Allah, W.H.; Osman, E.E.A.; Anwar, M.A.E.M.; Attia, H.N.; El Moghazy, S.M. Design, synthesis and docking studies of novel benzopyrone derivatives as anticonvulsants. Bioorg. Chem., 2020, 98, 103738.
[http://dx.doi.org/10.1016/j.bioorg.2020.103738] [PMID: 32179283]
[89]
Karataş, M.O.; Uslu, H.; Sarı, S.; Alagöz, M.A.; Karakurt, A.; Alıcı, B.; Bilen, C.; Yavuz, E.; Gencer, N.; Arslan, O. Coumarin or benzoxazinone based novel carbonic anhydrase inhibitors: Synthesis, molecular docking and anticonvulsant studies. J. Enzyme Inhib. Med. Chem., 2016, 31(5), 760-772.
[http://dx.doi.org/10.3109/14756366.2015.1063624] [PMID: 26207513]
[90]
Kozioł, E.; Jóźwiak, K.; Budzyńska, B.; de Witte, P.A.M.; Copmans, D.; Skalicka-Woźniak, K. Comparative antiseizure analysis of diverse natural coumarin derivatives in zebrafish. Int. J. Mol. Sci., 2021, 22(21), 11420.
[http://dx.doi.org/10.3390/ijms222111420] [PMID: 34768849]
[91]
Vazquez-Rodriguez, S.; Vilar, S.; Kachler, S.; Klotz, K.N.; Uriarte, E.; Borges, F.; Matos, M.J. Adenosine receptor ligands: Coumarin-Chalcone hybrids as modulating agents on the activity of hARs. Molecules, 2020, 25(18), 4306.
[http://dx.doi.org/10.3390/molecules25184306] [PMID: 32961824]
[92]
Adsule, P.V.; Chabukswar, A.R.; Nanaware, R. Design, synthesis, anti-inflammatory & anticonvulsant activity of substituted heterocyclic compounds. J. Pharm. Res. Int., 2021, 33, 96-111.
[http://dx.doi.org/10.9734/jpri/2021/v33i47B33100]
[93]
Lin, D.; Xiao, M.; Zhao, J.; Li, Z.; Xing, B.; Li, X.; Kong, M.; Li, L.; Zhang, Q.; Liu, Y.; Chen, H.; Qin, W.; Wu, H.; Chen, S. An overview of plant phenolic compounds and their importance in human nutrition and management of type 2 diabetes. Molecules, 2016, 21(10), 1374.
[http://dx.doi.org/10.3390/molecules21101374] [PMID: 27754463]
[94]
Mutha, R.E.; Tatiya, A.U.; Surana, S.J. Flavonoids as natural phenolic compounds and their role in therapeutics: An overview. Fut. J. Pharm. Sci., 2021, 7(1), 25.
[http://dx.doi.org/10.1186/s43094-020-00161-8] [PMID: 33495733]
[95]
Rahman, M.M.; Rahaman, M.S.; Islam, M.R.; Rahman, F.; Mithi, F.M.; Alqahtani, T.; Almikhlafi, M.A.; Alghamdi, S.Q.; Alruwaili, A.S.; Hossain, M.S.; Ahmed, M.; Das, R.; Emran, T.B.; Uddin, M.S. Role of phenolic compounds in human disease: Current knowledge and future prospects. Molecules, 2021, 27(1), 233.
[http://dx.doi.org/10.3390/molecules27010233] [PMID: 35011465]
[96]
Al Mamari, H.H. Phenolic Compounds: Classification, chemistry, and updated techniques of analysis and synthesis. In: Phenolic Compounds-Chemistry, Synthesis, Diversity, Non-Conventional Industrial, Pharmaceutical and Therapeutic Applications;; IntechOpen, 2021.
[97]
Da Guedes, E.; Ribeiro, L.R.; Carneiro, C.A.; Santos, A.M.F.; Brito, M.Á. De Andrade, HHN Anticonvulsant activity of trans -anethole in mice. BioMed Res. Int., 2022, 2022, 310-317.
[98]
Rauf, A.; Raza, M.; Saleem, M.; Ozgen, U.; Karaoglan, E.S.; Renda, G.; Palaska, E.; Orhan, I.E. Carbonic anhydrase and urease inhibitory potential of various plant phenolics using in vitro and in silico methods. Chem. Biodivers., 2017, 14(6), e1700024.
[http://dx.doi.org/10.1002/cbdv.201700024] [PMID: 28207990]
[99]
Liu, X.; Wang, C.Y.; Shao, C.L.; Wei, Y.X.; Wang, B.G.; Sun, L.L.; Zheng, C-J.; Guan, H-S. Chemical constituents from Sargassum pallidum (Turn.). C. Agardh. Biochem. Syst. Ecol., 2009, 37(2), 127-129.
[http://dx.doi.org/10.1016/j.bse.2009.01.009]
[100]
Iwashina, T.; Mizuno, T. Flavonoids and xanthones from the genus Iris: Phytochemistry, relationships with flower colors and taxonomy, and activities and function. Nat. Prod. Commun., 2020, 15(10)
[101]
Frezza, C.; Venditti, A.; Serafini, M.; Bianco, A. Phytochemistry, chemotaxonomy, ethnopharmacology, and nutraceutics of Lamiaceae. Studies in natural products chemistry; Elsevier, 2019, pp. 125-178.
[102]
Frezza, E. Patient-Centered Healthcare: Transforming the Relationship Between Physicians and Patients; CRC Press, 2019.
[http://dx.doi.org/10.4324/9780429032226]
[103]
Frezza, C.; Venditti, A.; De Vita, D.; Toniolo, C.; Franceschin, M.; Ventrone, A.; Tomassini, L.; Foddai, S.; Guiso, M.; Nicoletti, M.; Bianco, A.; Serafini, M. Phytochemistry, chemotaxonomy, and biological activities of the Araucariaceae family—A review. Plants, 2020, 9(7), 888.
[http://dx.doi.org/10.3390/plants9070888] [PMID: 32674354]
[104]
Frezza, C.; Venditti, A.; Giuliani, C.; Foddai, S.; Cianfaglione, K.; Maggi, F.; Fico, G.; Guiso, M.; Nicoletti, M.; Bianco, A.; Serafini, M. Occurrence of flavonoids in different Lamiaceae taxa for a preliminary study on their evolution based on phytochemistry. Biochem. Syst. Ecol., 2021, 96, 104247.
[http://dx.doi.org/10.1016/j.bse.2021.104247]
[105]
Zhu, L.; Yu, Z.; Zhong, G.; Ren, G. two new isoprenylated flavones from roots of Artocarpus styracifolius. Chem. Nat. Compd., 2022, 58(3), 426-428.
[http://dx.doi.org/10.1007/s10600-022-03701-1]
[106]
Orlova, A.A.; Whaley, A.K.; Ponkratova, A.O.; Balabas, O.A.; Smirnov, S.N.; Povydysh, M.N. Two new flavonol-bis-3,7-glucuronides from Geum rivale L. Phytochem. Lett., 2021, 42, 41-44.
[http://dx.doi.org/10.1016/j.phytol.2021.02.003]
[107]
Liu, H.; Jia, X.; Wang, H.; Xiao, C.; Du, C.; Tang, W. Flavanones from the fruit extract of Paulownia fortunei. Phytochem. Lett., 2021, 43, 196-199.
[http://dx.doi.org/10.1016/j.phytol.2021.04.009]
[108]
Lukaseder, B.; Vajrodaya, S.; Hehenberger, T.; Seger, C.; Nagl, M.; Lutz-Kutschera, G.; Robien, W.; Greger, H.; Hofer, O. Prenylated flavanones and flavanonols as chemical markers in Glycosmis species (Rutaceae). Phytochemistry, 2009, 70(8), 1030-1037.
[http://dx.doi.org/10.1016/j.phytochem.2009.05.007] [PMID: 19535116]
[109]
Luo, Y.; Jian, Y.; Liu, Y.; Jiang, S.; Muhammad, D.; Wang, W. Flavanols from nature: A phytochemistry and biological activity review. Molecules, 2022, 27(3), 719.
[http://dx.doi.org/10.3390/molecules27030719] [PMID: 35163984]
[110]
Alam, M.A.; Islam, P.; Subhan, N.; Rahman, M.M.; Khan, F.; Burrows, G.E.; Nahar, L.; Sarker, S.D. Potential health benefits of anthocyanins in oxidative stress related disorders. Phytochem. Rev., 2021, 20(4), 705-749.
[http://dx.doi.org/10.1007/s11101-021-09757-1]
[111]
Kaennakam, S.; Sukandar, E.R.; Rassamee, K.; Siripong, P.; Tip-pyang, S. Cytotoxic chalcones and isoflavones from the stems of Dalbergia velutina. Phytochem. Lett., 2019, 31, 187-191.
[http://dx.doi.org/10.1016/j.phytol.2019.04.005]
[112]
Li, Y.K.; Sun, J.Q.; Gao, X.M.; Lei, C. New isoprenylated aurones from the flowers of Rosa damascena. Helv. Chim. Acta, 2014, 97(3), 414-419.
[http://dx.doi.org/10.1002/hlca.201300336]
[113]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: An overview. J. Nutr. Sci., 2016, 5, e47.
[http://dx.doi.org/10.1017/jns.2016.41] [PMID: 28620474]
[114]
Iwashina, T. The structure and distribution of the flavonoids in plants. J. Plant Res., 2000, 113(3), 287-299.
[http://dx.doi.org/10.1007/PL00013940]
[115]
Liu, Y.; Shu, J.C.; Wang, M.F.; Xu, Z.J.; Yang, L.; Meng, X.W.; Duan, W.B.; Zhang, N.; Shao, F.; Liu, R.H.; Chen, L.Y. Melanoxylonin A-G, neoflavonoids from the heartwood of Dalbergia melanoxylon and their cardioprotective effects. Phytochemistry, 2021, 189, 112845.
[http://dx.doi.org/10.1016/j.phytochem.2021.112845] [PMID: 34171505]
[116]
Aydin, T.; Senturk, M.; Kazaz, C.; Cakir, A. Inhibitory effects and kinetic-docking studies of xanthohumol from Humulus lupulus cones against carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase. Nat. Prod. Commun., 2019, 14(10), 1934578X1988150.
[http://dx.doi.org/10.1177/1934578X19881503]
[117]
Wang, W.; Zhang, Y.; Yang, Y.; Gu, L. Network pharmacology and molecular docking to explore the mechanism of kangxian decoction for epilepsy; Evidence-based Complement Altern. Med, 2022.
[http://dx.doi.org/10.1155/2022/3333878]
[118]
da Silva, A.W.; Ferreira, M.K.A.; Pereira, L.R.; Rebouças, E.L.; Coutinho, M.R.; Dos, J. Combretum lanceolatum extract reverses anxiety and seizure behavior in adult zebrafish through GABAergic neurotransmission: An in vivo and in silico study. J. Biomol. Struct. Dyn., 2021, 0(0), 1-14.
[PMID: 34121622]
[119]
Aditama, R.; Mujahidin, D.; Syah, Y.M.; Hertadi, R. Docking and molecular dynamics simulation of carbonic anhydrase ii inhibitors from phenolic and flavonoid group. Procedia Chem., 2015, 16, 357-364.
[http://dx.doi.org/10.1016/j.proche.2015.12.064]
[120]
Redford, K.E.; Abbott, G.W. The ubiquitous flavonoid quercetin is an atypical KCNQ potassium channel activator. Commun. Biol., 2020, 3(1), 356.
[http://dx.doi.org/10.1038/s42003-020-1089-8] [PMID: 32641720]
[121]
Ahmed, H.; Khan, M.A.; Ali, Z.S.A.; Muhammad, S. In silico and in vivo: Evaluating the therapeutic potential of kaempferol, quercetin, and catechin to treat chronic epilepsy in a rat model. Front. Bioeng. Biotechnol., 2021, 9(November), 754952.
[http://dx.doi.org/10.3389/fbioe.2021.754952] [PMID: 34805114]
[122]
Huang, D.; Lv, Y.; Lu, C.; Zhang, B.; Fu, Z.; Huang, Y. Mechanism of Rhizoma coptidis in epilepsy with network pharmacology. Allergol. Immunopathol. (Madr.), 2022, 50(3), 138-150.
[http://dx.doi.org/10.15586/aei.v50i3.489] [PMID: 35527668]
[123]
Abdulrahman, H.L.; Uzairu, A.; Uba, S. QSAR, ligand based design and pharmacokinetic studies of parviflorons derivatives as anti-breast cancer drug compounds against MCF-7 cell line. Chemistry Africa, 2021, 4(1), 175-187.
[http://dx.doi.org/10.1007/s42250-020-00207-7]
[124]
Shirvani, P.; Fassihi, A. In silico design of novel FAK inhibitors using integrated molecular docking, 3D-QSAR and molecular dynamics simulation studies. J. Biomol. Struct. Dyn., 2022, 40(13), 5965-5982.
[125]
Kumar, A.; Agarwal, P.; Rathi, E.; Kini, S.G. Computer-aided identification of human carbonic anhydrase isoenzyme VII inhibitors as potential antiepileptic agents. J. Biomol. Struct. Dyn., 2022, 40(11), 4850-4865.
[PMID: 33345714]
[126]
Mauri, A.; Consonni, V.; Pavan, M.; Todeschini, R. Dragon software: An easy approach to molecular descriptor calculations. Match (Mulh.), 2006, 56(2), 237-248.
[127]
Willighagen, E.L.; Mayfield, J.W.; Alvarsson, J.; Berg, A.; Carlsson, L.; Jeliazkova, N. The Chemistry Development Kit (CDK) v2. 0: atom typing, depiction, molecular formulas, and substructure searching. J. Cheminform., 2017, 9(1), 1-19.
[128]
Landrum, G. RDKit: A software suite for cheminformatics, computational chemistry, and predictive modeling; Academic Press Cambridge, 2013.
[129]
Mazanetz, M.P.; Marmon, R.J.; Reisser, C.B.T.; Morao, I. Drug discovery applications for KNIME: an open source data mining platform. Curr. Top. Med. Chem., 2012, 12(18), 1965-1979.
[http://dx.doi.org/10.2174/156802612804910331] [PMID: 23110532]
[130]
Dou, J.; Yunus, A.P.; Tien Bui, D.; Merghadi, A.; Sahana, M.; Zhu, Z.; Chen, C.W.; Khosravi, K.; Yang, Y.; Pham, B.T. Assessment of advanced random forest and decision tree algorithms for modeling rainfall-induced landslide susceptibility in the Izu-Oshima Volcanic Island, Japan. Sci. Total Environ., 2019, 662, 332-346.
[http://dx.doi.org/10.1016/j.scitotenv.2019.01.221] [PMID: 30690368]
[131]
Monteiro, A.F.M.; Scotti, M.T.; Scotti, L. In silico studies of potentially active 2-amino-thiophenic derivatives against HIV-1. Int. J. Quantitative Structure-Property Relationships, 2020, 5(2), 100-119.
[http://dx.doi.org/10.4018/IJQSPR.2020040104]
[132]
Morales, J.F.; Chuguransky, S.; Alberca, L.N.; Alice, J.I.; Goicoechea, S.; Ruiz, M.E.; Bellera, C.L.; Talevi, A. Positive predictive value surfaces as a complementary tool to assess the performance of virtual screening methods. Mini Rev. Med. Chem., 2020, 20(14), 1447-1460.
[http://dx.doi.org/10.2174/1871525718666200219130229] [PMID: 32072906]
[133]
De Moura, É.P. Estudo in silico de flavonoides e análogos da família asteraceae contra a doença de alzheimer; Universidade Federal da Paraíba, 2021.
[134]
Sander, T.; Freyss, J.; von Korff, M.; Rufener, C. DataWarrior: an open-source program for chemistry aware data visualization and analysis. J. Chem. Inf. Model., 2015, 55(2), 460-473.
[http://dx.doi.org/10.1021/ci500588j] [PMID: 25558886]
[135]
Tamimi, A.F.; Juweid, M. Epidemiology and Outcome of Glioblastoma. 2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470003/
[http://dx.doi.org/10.15586/codon.glioblastoma.2017.ch8]
[136]
Malik, R.; Mehta, P.; Srivastava, S.; Singh, B.; Sharma, M. ADME prediction of N-pyridyl and pyrimidine benzamides as potent antiepileptic agents. J. Recept. Signal Transduct. Res., 2016, 37(3), 259-266.
[137]
Kerzare, D.R.; Menghani, S.S.; Rarokar, N.R.; Khedekar, P.B. Development of novel indole‐linked pyrazoles as anticonvulsant agents: A molecular hybridization approach. Arch. Pharm. (Weinheim), 2021, 354(1), 2000100.
[http://dx.doi.org/10.1002/ardp.202000100] [PMID: 32909304]
[138]
Cruciani, G.; Carosati, E.; De Boeck, B.; Ethirajulu, K.; Mackie, C.; Howe, T.; Vianello, R. MetaSite: understanding metabolism in human cytochromes from the perspective of the chemist. J. Med. Chem., 2005, 48(22), 6970-6979.
[http://dx.doi.org/10.1021/jm050529c] [PMID: 16250655]
[139]
Mestria, S.; Odoardi, S.; Federici, S.; Bilel, S.; Tirri, M.; Marti, M.; Strano Rossi, S. Metabolism study of N-Methyl 2-aminoindane (NM2AI) and determination of metabolites in biological samples by LC-HRMS. J. Anal. Toxicol., 2021, 45(5), 475-483.
[http://dx.doi.org/10.1093/jat/bkaa111] [PMID: 32860694]
[140]
Odoardi, S.; Mestria, S.; Biosa, G.; Arfè, R.; Tirri, M.; Marti, M.; Strano Rossi, S. Metabolism study and toxicological determination of mephtetramine in biological samples by liquid chromatography coupled with high‐resolution mass spectrometry. Drug Test. Anal., 2021, 13(8), 1516-1526.
[http://dx.doi.org/10.1002/dta.3044] [PMID: 33835674]
[141]
Scotti, L.; Scotti, M.T.; Pasqualoto, K.F.M.; Bolzani, V.S.; Ferreira, E.I. Molecular physicochemical parameters predicting antioxidant activity of Brazilian natural products. Rev. Bras. Farmacogn., 2009, 19(4), 908-913.
[http://dx.doi.org/10.1590/S0102-695X2009000600020]
[142]
Abbasi, H.; Fereidoonnezhad, M.; Mirveis, Z. Vilazodone-Tacrine Hybrids as Potential Anti-Alzheimer Agents: QSAR, Molecular Docking, and Molecular Dynamic; Simulation Studies: MD, 2021.
[143]
Rodrigues, C.; Hernández-González, J.; Pedrina, N.; Leite, V.; Bruni, A. In silico Evaluation of Cucurbit[6]uril as a Potential Detector for Cocaine and Its Adulterants Lidocaine, Caffeine, and Procaine. J. Braz. Chem. Soc., 2021, 32, 800-810.
[http://dx.doi.org/10.21577/0103-5053.20200231]
[144]
Armstrong, N.; Gouaux, E. Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core. Neuron, 2000, 28(1), 165-181.
[http://dx.doi.org/10.1016/S0896-6273(00)00094-5] [PMID: 11086992]
[145]
Zhao, Y.; Huang, G.; Wu, Q.; Wu, K.; Li, R.; Lei, J. Cryo-EM structures of apo and antagonist-bound human Cav3.1. Nature, 2019, 576(7787), 492-497.
[http://dx.doi.org/10.1038/s41586-019-1801-3] [PMID: 31766050]
[146]
Zhu, S.; Noviello, C.M.; Teng, J.; Walsh, R.M.; Kim, J.J.; Hibbs, R.E. Structure of a human synaptic GABAA receptor. 2018. Available from: https://www.nature.com/articles/s41586-018-0255-3
[http://dx.doi.org/10.1038/s41586-018-0255-3]
[147]
Motiwala, Z.; Aduri, N.G.; Shaye, H.; Han, G.W.; Lam, J.H.; Katritch, V. Structural basis of GABA reuptake inhibition. Available from: https://www.nature.com/articles/s41586-022-04814-x
[http://dx.doi.org/10.1038/s41586-022-04814-x]
[148]
Lind, G.E.; Mou, T.C.; Tamborini, L.; Pomper, M.G.; De Micheli, C.; Conti, P.; Pinto, A.; Hansen, K.B. Structural basis of subunit selectivity for competitive NMDA receptor antagonists with preference for GluN2A over GluN2B subunits. Proc. Natl. Acad. Sci. USA, 2017, 114(33), E6942-E6951. Available from: https://www.pnas.org/doi/abs/10.1073/pnas.1707752114
[http://dx.doi.org/10.1073/pnas.1707752114] [PMID: 28760974]
[149]
Ghosh, S.; Sinha, J.K.; Khan, T.; Devaraju, K.S.; Singh, P.; Vaibhav, K.; Gaur, P. Pharmacological and therapeutic approaches in the treatment of epilepsy. Biomedicines, 2021, 9(5), 470.
[http://dx.doi.org/10.3390/biomedicines9050470] [PMID: 33923061]
[150]
Maru, A. Molecular docking study of new-Mannich bases derived from pyrollidine-2, 5-dione as anticonvulsant agents. Int. J. Pharm. Sci. Res., 2020, 11(3), 1243-1248.
[151]
Zafar, S.; Jabeen, I. GRID-independent molecular descriptor analysis and molecular docking studies to mimic the binding hypothesis of γ-aminobutyric acid transporter 1 (GAT1) inhibitors. PeerJ, 2019, 7(1), e6283.
[http://dx.doi.org/10.7717/peerj.6283] [PMID: 30723616]
[152]
Thomsen, R.; Christensen, M.H. MolDock: a new technique for high-accuracy molecular docking. J. Med. Chem., 2006, 49(11), 3315-3321.
[http://dx.doi.org/10.1021/jm051197e] [PMID: 16722650]
[153]
Schlosser, J.; Rarey, M. Beyond the virtual screening paradigm: structure-based searching for new lead compounds. J. Chem. Inf. Model., 2009, 49(4), 800-809.
[http://dx.doi.org/10.1021/ci9000212] [PMID: 19354328]
[154]
Dong, N.Q.; Lin, H.X. Contribution of phenylpropanoid metabolism to plant development and plant-environment interactions. J. Integr. Plant Biol., 2021, 63(1), 180-209.
[http://dx.doi.org/10.1111/jipb.13054] [PMID: 33325112]
[155]
Vogt, T. Phenylpropanoid Biosynthesis. Mol. Plant, 2010, 3(1), 2-20. Available from: https://www.sciencedirect.com/science/article/pii/S1674205214603944
[http://dx.doi.org/10.1093/mp/ssp106] [PMID: 20035037]
[156]
Pieretti, S.; Saviano, A.; Mollica, A.; Stefanucci, A.; Aloisi, A.M.; Nicoletti, M. Anti-Inflammatory properties. 2022. Available from: https://en.wikipedia.org/wiki/Anti-inflammatory
[157]
Santana, F.P.R.; da Silva, R.C.; Ponci, V.; Pinheiro, A.J.M.C.R.; Olivo, C.R.; Caperuto, L.C.; Arantes-Costa, F.M.; Claudio, S.R.; Ribeiro, D.A.; Tibério, I.F.L.C.; Lima-Neto, L.G.; Lago, J.H.G.; Prado, C.M. Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways. Biochem. Pharmacol., 2020, 180, 114175. Available from: https://www.sciencedirect.com/science/article/pii/S0006295220304111
[http://dx.doi.org/10.1016/j.bcp.2020.114175] [PMID: 32717226]
[158]
Li, Y.; Lan, X.; Wang, S.; Cui, Y.; Song, S.; Zhou, H. Serial five-membered lactone ring ions in the treatment of Alzheimer’s diseases-comprehensive profiling of arctigenin metabolites and network analysis [internet]. Frontiers in Pharmacology., 2022, 13. Available from: https://www.frontiersin.org/articles/10.3389/fphar.2022.1065654
[159]
Jayaraj, P.B.; Jain, S. Ligand based virtual screening using SVM on GPU. Comput. Biol. Chem., 2019, 83, 107143.
[http://dx.doi.org/10.1016/j.compbiolchem.2019.107143] [PMID: 31743833]
[160]
Shayanfar, S.; Shayanfar, A. Comparison of various methods for validity evaluation of QSAR models. BMC Chem., 2022, 16(1), 63. Available from: https://bmcchem-biomedcentral-com.ez15.periodicos.capes.gov.br/articles/10.1186/s13065-022-00856-4
[http://dx.doi.org/10.1186/s13065-022-00856-4] [PMID: 35999611]
[161]
Chitre, T.S.; Patil, S.M.; Sujalegaonkar, A.G.; Asgaonkar, K.D. Designing of thiazolidin-4-one pharmacophore using QSAR studies for anti-HIV activity. Indian J Pharm Edu Res., 2021, 55(2), 581-589.
[http://dx.doi.org/10.5530/ijper.55.2.97]
[162]
Chicco, D.; Warrens, M.J.; Jurman, G. The matthews correlation coefficient (MCC) is more informative than Cohen’s kappa and brier score in binary classification assessment. IEEE Access, 2021, 9, 78368-78381.
[http://dx.doi.org/10.1109/ACCESS.2021.3084050]
[163]
Chicco, D.; Tötsch, N.; Jurman, G. The Matthews correlation coefficient (MCC) is more reliable than balanced accuracy, bookmaker informedness, and markedness in two-class confusion matrix evaluation. BioData Min., 2021, 14(1), 13.
[http://dx.doi.org/10.1186/s13040-021-00244-z] [PMID: 33541410]
[164]
Fanjul-Hevia, A.; González-Manteiga, W.; Pardo-Fernández, J.C. A non-parametric test for comparing conditional ROC curves. Comput. Stat. Data Anal., 2021, 157, 107146. Available from: https://www.sciencedirect.com/science/article/pii/S0167947320302371
[http://dx.doi.org/10.1016/j.csda.2020.107146]
[165]
Alonso, R.; Nakas, C.T.; Carmen Pardo, M. A study of indices useful for the assessment of diagnostic markers in non-parametric ROC curve analysis. Commun. Stat. Simul. Comput., 2020, 49(8), 2102-2113.
[http://dx.doi.org/10.1080/03610918.2018.1511806]
[166]
Carrington, A.M.; Manuel, D.G.; Fieguth, P.W.; Ramsay, T.; Osmani, V.; Wernly, B.; Bennett, C.; Hawken, S.; Magwood, O.; Sheikh, Y.; McInnes, M.; Holzinger, A. Deep ROC analysis and AUC as balanced average accuracy, for improved classifier selection, audit and explanation. IEEE Trans. Pattern Anal. Mach. Intell., 2023, 45(1), 329-341.
[http://dx.doi.org/10.1109/TPAMI.2022.3145392] [PMID: 35077357]
[167]
Bellera, C.L.; Talevi, A. Quantitative structure-activity relationship models for compounds with anticonvulsant activity. Expert Opin. Drug Discov., 2019, 14(7), 653-665.
[http://dx.doi.org/10.1080/17460441.2019.1613368] [PMID: 31072145]
[168]
dos Santos Maia, M.; Raimundo e Silva, J.P.; de Lima Nunes, T.A.; Saraiva de Sousa, J.M.; Soares, R.G.C.; Messias, M.A.F. Virtual screening and the in vitro assessment of the antileishmanial activity of lignans. Molecules, 2020, 25, 1-33.
[http://dx.doi.org/10.3390/molecules25102281]
[169]
Unadkat, V.; Rohit, S.; Parikh, P.; Patel, K.; Sanna, V.; Singh, S. Identification of 1,2,4-oxadiazoles-based novel EGFR inhibitors: molecular dynamics simulation-guided identification and in vitro ADME studies. OncoTargets Ther., 2022, 15, 479-495.
[http://dx.doi.org/10.2147/OTT.S357765] [PMID: 35535170]
[170]
Soares, J.X.; Santos, Á.; Fernandes, C.; Pinto, M.M.M. Liquid chromatography on the different methods for the determination of lipophilicity: An essential analytical tool in medicinal chemistry. chemosens., 2022. Available from: https://www.mdpi.com/2227-9040/10/8/340/htm
[171]
Wang, Z.; Felstead, H.R.; Troup, R.I.; Linclau, B.; Williamson, P.T.F. Lipophilicity modulations by fluorination correlate with membrane partitioning. Angew. Chem. Int. Ed., 2023, 62(21), e202301077.
[http://dx.doi.org/10.1002/anie.202301077] [PMID: 36932824]
[172]
Sevastos, A.A.; Baker, C.M.; Taylor, P. A simple method for predicting alkane‐water partition coefficients of surfactants. J. Surfactants Deterg., 2022, 25(1), 53-61.
[http://dx.doi.org/10.1002/jsde.12545]
[173]
Pan-On, S.; Tiyaboonchai, W. Development, characterization and Caco-2 cells absorption of curcumin solid dispersion for oral administration. J. Drug Deliv. Sci. Technol., 2023, 86, 104574.
[http://dx.doi.org/10.1016/j.jddst.2023.104574]
[174]
Azman, M.; Sabri, A.H.; Anjani, Q.K.; Mustaffa, M.F.; Hamid, K.A. Intestinal absorption Study: Challenges and absorption enhancement strategies in improving oral drug delivery. Pharmaceuticals (Basel), 2022, 15(8), 975.
[http://dx.doi.org/10.3390/ph15080975] [PMID: 36015123]
[175]
lenin, S.; sujatha, R.; Palanisamy, S. Pharmacological properties and bioavailability studies of 3-methyl quinoline. Int. J. Pharma Bio Sci., 2022, 12(1), 100-104.
[http://dx.doi.org/10.22376/ijpbs/lpr.2022.12.1.L100-104]
[176]
Sharma, S.; Prasad, B. Meta-analysis of food effect on oral absorption of efflux transporter substrate drugs: Does delayed gastric emptying influence drug transport kinetics? Pharmaceutics, 2021, 13(7), 1035.
[http://dx.doi.org/10.3390/pharmaceutics13071035] [PMID: 34371727]
[177]
Dudhipala, N.; Ettireddy, S.; Youssef, A.A.A.; Puchchakayala, G. Development and in vivo pharmacokinetic and pharmacodynamic evaluation of an oral innovative cyclodextrin complexed lipid nanoparticles of irbesartan formulation for enhanced bioavailability. Nanotheranostics, 2023, 7(1), 117-127. Available from: https://www.ntno.org/v07p0117.htm
[http://dx.doi.org/10.7150/ntno.78102] [PMID: 36593793]
[178]
Morak-Młodawska, B.; Jeleń, M.; Martula, E.; Korlacki, R. Study of lipophilicity and ADME properties of 1,9-diazaphenothiazines with anticancer action. Int. J. Mol. Sci., 2023, 24(8), 6970.
[http://dx.doi.org/10.3390/ijms24086970] [PMID: 37108135]
[179]
Müller, J.; Martins, A.; Csábi, J.; Fenyvesi, F.; Könczöl, Á.; Hunyadi, A.; Balogh, G.T. BBB penetration-targeting physicochemical lead selection: Ecdysteroids as chemo-sensitizers against CNS tumors. Eur. J. Pharm. Sci., 2017, 96, 571-577. Available from: https://www.sciencedirect.com/science/article/pii/S0928098716304730
[http://dx.doi.org/10.1016/j.ejps.2016.10.034] [PMID: 27810561]
[180]
Vilar, S.; Chakrabarti, M.; Costanzi, S. Prediction of passive blood-brain partitioning: Straightforward and effective classification models based on in silico derived physicochemical descriptors. J. Mol. Graph. Model., 2010, 28(8), 899-903.
[http://dx.doi.org/10.1016/j.jmgm.2010.03.010] [PMID: 20427217]
[181]
van de Waterbeemd, H.; Camenisch, G.; Folkers, G.; Chretien, J.R.; Raevsky, O.A. Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J. Drug Target., 1998, 6(2), 151-165.
[http://dx.doi.org/10.3109/10611869808997889] [PMID: 9886238]
[182]
Fu, X.; He, S.; Du, L.; Lv, Z.; Zhang, Y.; Zhang, Q.; Wang, Y. Using chemical bond-based method to predict site of metabolism for five biotransformations mediated by CYP 3A4, 2D6, and 2C9. Biochem. Pharmacol., 2018, 152, 302-314.
[http://dx.doi.org/10.1016/j.bcp.2018.03.024] [PMID: 29588194]
[183]
Esteves, F.; Rueff, J.; Kranendonk, M. The central role of cytochrome P450 in xenobiotic metabolism-a brief review on a fascinating enzyme family. J. Xenobiot., 2021, 11(3), 94-114.
[http://dx.doi.org/10.3390/jox11030007] [PMID: 34206277]
[184]
Awasthi, N.; Yadav, R.; Kumar, D. Metabolism of 8-aminoquinoline (8AQ) primaquine via aromatic hydroxylation step mediated by cytochrome P450 enzyme using density functional theory. J. Organomet. Chem., 2022, 957, 122154.
[http://dx.doi.org/10.1016/j.jorganchem.2021.122154]
[185]
Coleman, T.; Kirk, A.M.; Lee, J.H.Z.; Doherty, D.Z.; Bruning, J.B.; Krenske, E.H.; De Voss, J.J.; Bell, S.G. Different geometric requirements for cytochrome P450-catalyzed aliphatic versus aromatic hydroxylation results in chemoselective oxidation. ACS Catal., 2022, 12(2), 1258-1267.
[http://dx.doi.org/10.1021/acscatal.1c05483]
[186]
Wong, S.H.; Bell, S.G.; De Voss, J.J. P450 catalysed dehydrogenation. Pure Appl. Chem., 2017, 89(6), 841-852.
[http://dx.doi.org/10.1515/pac-2016-1216]
[187]
You, G.; Yang, R.; Wei, Y.; Hu, W.; Gan, L.; Xie, C.; Zheng, Z.; Liu, Z.; Liao, R.; Ye, L. The detoxification effect of cytochrome P450 3A4 on gelsemine-induced toxicity. Toxicol. Lett., 2021, 353, 34-42.
[http://dx.doi.org/10.1016/j.toxlet.2021.10.003] [PMID: 34627953]
[188]
Iacopetta, D.; Ceramella, J.; Catalano, A.; Scali, E.; Scumaci, D.; Pellegrino, M.; Aquaro, S.; Saturnino, C.; Sinicropi, M.S. Impact of cytochrome P450 enzymes on the phase i metabolism of drugs. Appl. Sci. (Basel), 2023, 13(10), 6045.
[http://dx.doi.org/10.3390/app13106045]
[189]
Zheng, L.; Meng, J.; Jiang, K.; Lan, H.; Wang, Z.; Lin, M.; Li, W.; Guo, H.; Wei, Y.; Mu, Y. Improving protein-ligand docking and screening accuracies by incorporating a scoring function correction term. Brief. Bioinform., 2022, 23(3), bbac051.
[http://dx.doi.org/10.1093/bib/bbac051] [PMID: 35289359]
[190]
Abookleesh, F.; Mosa, F.E.S.; Barakat, K.; Ullah, A. Assessing molecular docking tools to guide the design of polymeric materials formulations: A case study of canola and soybean protein. Polymers (Basel), 2022, 14(17), 3690.
[http://dx.doi.org/10.3390/polym14173690] [PMID: 36080764]
[191]
Biswas, P.; Hany, R.O.; Ahmed, K.D.; Ahmed, M.N.; Nahar, N.; Jahan, R.; Hasan, Z.M.N.; Paul, T.K.; Hasan, A.; Bondhon, T.A.; Jannat, K. Evaluation of melongosides as potential inhibitors ofNS2B-NS3 activator-protease of dengue virus (Serotype 2) by using molecular docking and dynamics simulation approach. J. Tropical Med., 2022, 2022
[http://dx.doi.org/10.1155/2022/7111786]
[192]
Son, Y.H.; Shin, D.H.; Han, J.W.; Won, S.H.; Kam, T.E. GNNbased antibody structure prediction using quaternion and euler angle combined representation. In 2022 IEEE International Conference on Consumer Electronics-Asia (ICCE-Asia) 2022.
[http://dx.doi.org/10.1109/ICCE-Asia57006.2022.9954877]
[193]
Plewczynski, D.; Łażniewski, M.; Grotthuss, M.V.; Rychlewski, L.; Ginalski, K. VoteDock: Consensus docking method for prediction of protein-ligand interactions. J. Comput. Chem., 2011, 32(4), 568-581. Available from: https://onlinelibrary.wiley.com/doi/full/10.1002/jcc.21642
[http://dx.doi.org/10.1002/jcc.21642] [PMID: 20812324]
[194]
Li, D.D.; Meng, X.F.; Wang, Q.; Yu, P.; Zhao, L.G.; Zhang, Z.P.; Wang, Z.Z.; Xiao, W. Consensus scoring model for the molecular docking study of mTOR kinase inhibitor. J. Mol. Graph. Model., 2018, 79, 81-87.
[http://dx.doi.org/10.1016/j.jmgm.2017.11.003] [PMID: 29154212]
[195]
Wang, J.Y.; Zhao, L.X.; Shi, J.; Gao, S.; Ye, F.; Fu, Y. Discovery of novel HPPD inhibitors based on a combination strategy of pharmacophore, consensus docking and molecular dynamics. J. Mol. Liq., 2022, 362, 119683.
[http://dx.doi.org/10.1016/j.molliq.2022.119683]
[196]
dos Santos, M.M.; Soares, R.G.C.; Silva, C.A.B.; Scotti, L.; Scotti, M.T. Consensus analyses in molecular docking studies applied to medicinal chemistry. Mini Rev. Med. Chem., 2020, 20(14), 1322-1340.
[http://dx.doi.org/10.2174/1389557520666200204121129] [PMID: 32013847]
[197]
Chen, T.S.; Huang, T.H.; Lai, M.C.; Huang, C.W. The role of glutamate receptors in epilepsy. Biomedicines, 2023, 11(3), 783.
[http://dx.doi.org/10.3390/biomedicines11030783] [PMID: 36979762]
[198]
Dossi, E.; Huberfeld, G. GABAergic circuits drive focal seizures. Neurobiol. Dis., 2023, 180, 106102. Available from: https://www.sciencedirect.com/science/article/pii/S096999612300116X
[http://dx.doi.org/10.1016/j.nbd.2023.106102] [PMID: 36977455]
[199]
Valipour, M.; Naderi, N.; Heidarli, E.; Shaki, F.; Motafeghi, F.; Talebpour Amiri, F.; Emami, S.; Irannejad, H. Design, synthesis and biological evaluation of naphthalene-derived (arylalkyl)azoles containing heterocyclic linkers as new anticonvulsants: A comprehensive in silico, in vitro, and in vivo study. Eur. J. Pharm. Sci., 2021, 166, 105974.
[http://dx.doi.org/10.1016/j.ejps.2021.105974] [PMID: 34390829]
[200]
Emami, S.; Valipour, M.; Kazemi, K.F.; Sadati-Ashrafi, F.; Rasoulian, M.; Ghasemian, M.; Tajbakhsh, M.; Masihi, P.H.; Shakiba, A.; Irannejad, A.N. Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents. Bioorg. Chem., 2021, 112, 104943.
[201]
El-Helby, A.G.A.; Ayyad, R.R.A.; El-Adl, K.; Elkady, H. Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design, synthesis, anticonvulsant evaluation, ADMET profile and molecular docking. Mol. Divers., 2019, 23(2), 283-298.
[http://dx.doi.org/10.1007/s11030-018-9871-y] [PMID: 30168051]
[202]
Andrade, JC; Monteiro, ÁB; Andrade, HHN; Gonzaga, TKSN; Silva, PR; Alves, DN Castro, R.D.; Maia, M.S.; Scotti, M.T.; Sousa, D.P.; Almeida, R.N. Involvement of GABA A receptors in the anxiolytic-like effect of hydroxycitronellal. BioMed Res. Int., 2021, 2021
[203]
Scotti, L.; Lustoza Rodrigues, T.C.M.; de Sousa, N.F.; dos Santos, A.M.F.; Aires Guimarães, R.D.; Scotti, M.T. Challenges and discoveries in polypharmacology of neurodegenerative diseases. Curr. Top. Med. Chem., 2023, 23(5), 349-370.
[http://dx.doi.org/10.2174/1568026623666230126112628] [PMID: 36703583]
[204]
Rodrigues, T.C.M.; de Moura, J.P.; dos Santos, A.M.F.; Monteiroa, A.F.M.; Lopes, S.M.; Scotti, M.T.; Scotti, L. Epileptic targets and drugs: A mini-review. Curr. Drug Targets, 2023, 24(3), 212-224. Available from: https://www.eurekaselect.com/209186/article

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