Recent Advancements and SAR Studies of Synthetic Coumarins as
MAO-B Inhibitors: An Updated Review

Prabhjot      Kaur; Naresh   Kumar   Rangra

doi:10.2174/0113895575290599240503080025

Abstract

Background: The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage.

Objective: The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles.

Methods: The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer’s Disease and Parkinson’s Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study.

Results: The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer’s Disease and Parkinson’s Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted.

Conclusion: Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer’s Disease and Parkinson’s Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

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[1]
Liu, L.; Zhang, Y.; Tang, L.; Zhong, H.; Danzeng, D.; Liang, C.; Liu, S. The neuroprotective effect of Byu d Mar 25 in LPS-induced alzheimer’s disease mice model. Evid. Based Complement. Alternat. Med.,  2021, 2021, 1-12.
 [http://dx.doi.org/10.1155/2021/8879014] [PMID:  33727946]

[2]
Zeng, W.; Yu, L.; Wu, J.; Wang, F.; Liu, X.; Ren, S.; Zhang, D.; Lian, B.; Hu, M.; Cao, L. Clinical characteristics and long-term follow-up outcomes of myelin oligodendrocyte glycoprotein antibody-associated disease in Han Chinese participants. Medicine,  2023, 102(40), e35391.
 [http://dx.doi.org/10.1097/MD.0000000000035391] [PMID:  37800805]

[3]
Yi, J.; Li, L.; Yin, Z.; Quan, Y.; Tan, R.; Chen, S.; Lang, J.; Li, J.; Zeng, J.; Li, Y.; Sun, Z.; Zhao, J. Polypeptide from moschus suppresses lipopolysaccharide-induced inflammation by inhibiting NF-κ B-ROS/NLRP3 pathway. Chin. J. Integr. Med.,  2023, 29(10), 895-904.
 [http://dx.doi.org/10.1007/s11655-023-3598-z] [PMID:  37542626]

[4]
Cho, H.U.; Kim, S.; Sim, J.; Yang, S.; An, H.; Nam, M.H.; Jang, D.P.; Lee, C.J. Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis. Exp. Mol. Med.,  2021, 53(7), 1148-1158.
 [http://dx.doi.org/10.1038/s12276-021-00646-3] [PMID:  34244591]

[5]
Liu, Y.; Li, H.; Wang, X.; Huang, J.; Zhao, D.; Tan, Y.; Zhang, Z.; Zhang, Z.; Zhu, L.; Wu, B.; Chen, Z.; Peng, W. Anti-alzheimers molecular mechanism of icariin: Insights from gut microbiota, metabolomics, and network pharmacology. J. Transl. Med.,  2023, 21(1), 277-0.
 [http://dx.doi.org/10.1186/s12967-023-04137-z] [PMID:  37095548]

[6]
Patil, P.O.; Bari, S.B.; Firke, S.D.; Deshmukh, P.K.; Donda, S.T.; Patil, D.A. A comprehensive review on synthesis and designing aspects of coumarin derivatives as monoamine oxidase inhibitors for depression and Alzheimer’s disease. Bioorg. Med. Chem.,  2013, 21(9), 2434-2450.
 [http://dx.doi.org/10.1016/j.bmc.2013.02.017] [PMID:  23517722]

[7]
Behl, T.; Kaur, D.; Sehgal, A.; Singh, S.; Sharma, N.; Zengin, G.; Cioara, A.F.L.; Toma, M.M.; Bungau, S.; Bumbu, A.G. Role of monoamine oxidase activity in Alzheimer’s disease: an insight into the therapeutic potential of inhibitors. Molecules,  2021, 26(12), 3724.
 [http://dx.doi.org/10.3390/molecules26123724] [PMID:  34207264]

[8]
Edmondson, D.E.; Binda, C.; Mattevi, A. Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B. Arch. Biochem. Biophys.,  2007, 464(2), 269-276.
 [http://dx.doi.org/10.1016/j.abb.2007.05.006] [PMID:  17573034]

[9]
Regensburger, M.; Ip, C.W.; Kohl, Z.; Schrader, C.; Urban, P.P.; Kassubek, J.; Jost, W.H. Clinical benefit of MAO-B and COMT inhibition in Parkinson’s disease: Practical considerations. J. Neural Transm.,  2023, 130(6), 847-861.
 [http://dx.doi.org/10.1007/s00702-023-02623-8] [PMID:  36964457]

[10]
Liu, H; Li, B; Xi, P; Liu, Y; Li, F; Lang, Y; Tang, R; Ma, N; He, J Time-varying functional connectivity of rat brain during bipedal walking on unexpected terrain. Cyborg and Bionic Systems.,  2023, 4, 0017.
 [http://dx.doi.org/10.34133/cbsystems.0017]

[11]
Li, J.; Luo, J.; Liu, L.; Fu, H.; Tang, L. The genetic association between apolipoprotein E gene polymorphism and Parkinson disease. Medicine,  2018, 97(43), e12884-e0.
 [http://dx.doi.org/10.1097/MD.0000000000012884] [PMID:  30412083]

[12]
Yeh, CH; Zhang, C; Shi, W; Lo, MT; Tinkhauser, G; Oswal, A Cross-frequency coupling and intelligent neuromodulation. Cyborg Bion. Syst.,  2023, 4, 0034.
 [http://dx.doi.org/10.34133/cbsystems.0034]

[13]
Boulaamane, Y.; Kandpal, P.; Chandra, A.; Britel, M.R.; Maurady, A. Chemical library design, QSAR modeling and molecular dynamics simulations of naturally occurring coumarins as dual inhibitors of MAO-B and AChE. J. Biomol. Struct. Dyn.,  2023, 29, 1-8.
 [http://dx.doi.org/10.1080/07391102.2023.2260879] [PMID:  37199265]

[14]
Pisani, L.; Catto, M.; Muncipinto, G.; Nicolotti, O.; Carrieri, A.; Rullo, M.; Stefanachi, A.; Leonetti, F.; Altomare, C. A twenty-year journey exploring coumarin-based derivatives as bioactive molecules. Front Chem.,  2022, 10, 1002547.
 [http://dx.doi.org/10.3389/fchem.2022.1002547] [PMID:  36300022]

[15]
Mellado, M.; Mella, J.; González, C.; Viña, D.; Uriarte, E.; Matos, M.J. 3-Arylcoumarins as highly potent and selective monoamine oxidase B inhibitors: Which chemical features matter? Bioorg. Chem.,  2020, 101, 103964.
 [http://dx.doi.org/10.1016/j.bioorg.2020.103964] [PMID:  32474182]

[16]
Seo, W.D.; Kim, J.Y.; Ryu, H.W.; Kim, J.H.; Han, S.I.; Ra, J.E.; Seo, K.H.; Jang, K.C.; Lee, J.H. Identification and characterisation of coumarins from the roots of Angelica dahurica and their inhibitory effects against cholinesterase. J. Funct. Foods,  2013, 5(3), 1421-1431.
 [http://dx.doi.org/10.1016/j.jff.2013.05.011]

[17]
Iranshahi, M.; Kalategi, F.; Sahebkar, A.; Sardashti, A.; Schneider, B. New sesquiterpene coumarins from the roots of Ferula flabelliloba. Pharm. Biol.,  2010, 48(2), 217-220.
 [http://dx.doi.org/10.3109/13880200903019226] [PMID:  20645844]

[18]
Peng, W.W.; Zheng, Y.Q.; Chen, Y.S.; Zhao, S.M.; Ji, C.J.; Tan, N.H. Coumarins from roots of Clausena excavata. J. Asian Nat. Prod. Res.,  2013, 15(3), 215-220.
 [http://dx.doi.org/10.1080/10286020.2012.758635] [PMID:  23327112]

[19]
Naseri, M.; Monsef-Esfehani, H.R.; Saeidnia, S.; Dastan, D.; Gohari, A.R. Antioxidative coumarins from the roots of ferulago subvelutina. Asian J. Chem.,  2013, 25(4), 1875-1878.
 [http://dx.doi.org/10.14233/ajchem.2013.13208]

[20]
Bai, Y.; Li, D.; Zhou, T.; Qin, N.; Li, Z.; Yu, Z.; Hua, H. Coumarins from the roots of Angelica dahurica with antioxidant and antiproliferative activities. J. Funct. Foods,  2016, 20, 453-462.
 [http://dx.doi.org/10.1016/j.jff.2015.11.018]

[21]
Joshi, K.R.; Devkota, H.P.; Yahara, S. Chemical analysis of flowers of Bombax ceiba from Nepal. Nat. Prod. Commun.,  2013, 8(5), 1934578X1300800.
 [http://dx.doi.org/10.1177/1934578X1300800508]

[22]
Sukumaran, S.; Kiruba, S.; Mahesh, M.; Nisha, S.R.; Miller, P.Z.; Ben, C.P.; Jeeva, S. Phytochemical constituents and antibacterial efficacy of the flowers of peltophorum pterocarpum (DC.) baker ex heyne. Asian Pac. J. Trop. Med.,  2011, 4(9), 735-738.
 [http://dx.doi.org/10.1016/S1995-7645(11)60183-1] [PMID:  21967698]

[23]
Kicel, A.; Wolbis, M. Coumarins from the flowers of Trifolium repens. Chem. Nat. Compd.,  2012, 48(1), 130-132.
 [http://dx.doi.org/10.1007/s10600-012-0179-3]

[24]
Molnar, M.; Lončarić, M.; Kovač, M. Green chemistry approaches to the synthesis of coumarin derivatives. Curr. Org. Chem.,  2020, 24(1), 4-43.
 [http://dx.doi.org/10.2174/1385272824666200120144305]

[25]
Sharma, D.; Dhayalan, V.; Chatterjee, R.; Khatravath, M.; Dandela, R. Recent advances in the synthesis of coumarin and its derivatives by using aryl propiolates. ChemistrySelect,  2022, 7(4), e202104299.
 [http://dx.doi.org/10.1002/slct.202104299]

[26]
Vekariya, R.H.; Patel, H.D. Recent advances in the synthesis of coumarin derivatives via Knoevenagel condensation: A review. Synth. Commun.,  2014, 44(19), 2756-2788.
 [http://dx.doi.org/10.1080/00397911.2014.926374]

[27]
He, X.; Yan, Z.; Hu, X.; Zuo, Y.; Jiang, C.; Jin, L.; Shang, Y. FeCl 3 -catalyzed cascade reaction: An efficient approach to functionalized coumarin derivatives. Synth. Commun.,  2014, 44(10), 1507-1514.
 [http://dx.doi.org/10.1080/00397911.2013.862833]

[28]
Akwu, N.A.; Lekhooa, M.; Deqiang, D.; Aremu, A.O. Antidepressant effects of coumarins and their derivatives: A critical analysis of research advances. Eur. J. Pharmacol.,  2023, 956, 175958.
 [http://dx.doi.org/10.1016/j.ejphar.2023.175958] [PMID:  37543158]

[29]
Enríquez, R.F.; Lago, C.M.C.; Besada, P.; Pena, A.M.; Terán, T.I.; Viña, D.; Fontenla, J.Á.; Sturlese, M.; Moro, S.; Quezada, E.; Terán, C. Novel coumarin-pyridazine hybrids as selective MAO-B inhibitors for the Parkinson’s disease therapy. Bioorg. Chem.,  2020, 104, 104203.
 [http://dx.doi.org/10.1016/j.bioorg.2020.104203] [PMID:  32932120]

[30]
Rad, S.J.; Martins, C.N.; Jornet, L.P.; Lopez, E.P.; Harun, N.; Yeskaliyeva, B.; Beyatli, A.; Sytar, O.; Shaheen, S.; Sharopov, F. Taheri, Y Natural coumarins: Exploring the pharmacological complexity and underlying molecular mechanisms. Oxid. Med. Cell. Longev.,  2021, 2021, 6492346.
 [http://dx.doi.org/10.1155/2021/6492346]

[31]
Wu, Y.; Xu, J.; Liu, Y.; Zeng, Y.; Wu, G. A review on anti-tumor mechanisms of coumarins. Front. Oncol.,  2020, 10, 592853.
 [http://dx.doi.org/10.3389/fonc.2020.592853] [PMID:  33344242]

[32]
Wadsworth, D.; Sullivan, E.; Jacky, T.; Sprague, T.; Feinman, H.; Kim, J. A review of indications and comorbidities in which warfarin may be the preferred oral anticoagulant. J. Clin. Pharm. Ther.,  2021, 46(3), 560-570.
 [http://dx.doi.org/10.1111/jcpt.13343] [PMID:  33393699]

[33]
El-Saghier, A.M.M.; Khodairy, A. New synthetic approaches to condensed and spiro coumarins: coumarin-3-thiocarboxamide as building block for the synthesis of condensed and spiro coumarins. Phosphorus Sulfur Silicon Relat. Elem.,  2000, 160(1), 105-119.
 [http://dx.doi.org/10.1080/10426500008043675]

[34]
Khokhlenkova, N.V.; Buryak, M.V.; Povrozina, O.V.; Kamina, T.V. Principles of the urolithiasis phytotherapy. Res. J. Pharm. Technol.,  2019, 12(9), 4559-4564.
 [http://dx.doi.org/10.5958/0974-360X.2019.00784.4]

[35]
Michel, J.B. Phylogenic determinants of cardiovascular frailty, focus on hemodynamics and arterial smooth muscle cells. Physiol. Rev.,  2020, 100(4), 1779-1837.
 [http://dx.doi.org/10.1152/physrev.00022.2019] [PMID:  31999509]

[36]
Dabhi, R.C.; Sharma, V.S.; Arya, P.S.; Patel, U.P.; Shrivastav, P.S.; Maru, J.J. Coumarin functionalized dimeric mesogens for promising anticoagulant activity: Tuning of liquid crystalline property. J. Mol. Struct.,  2023, 1283, 135336.
 [http://dx.doi.org/10.1016/j.molstruc.2023.135336]

[37]
Siddiqi, A.; Rani, M.; Bansal, P.; Rizvi, M.M.A. Renal cell carcinoma management: A step to nano-chemoprevention. Life Sci.,  2022, 308, 120922-0.
 [http://dx.doi.org/10.1016/j.lfs.2022.120922] [PMID:  36058262]

[38]
Reddy, D.S.; Kongot, M.; Kumar, A. Coumarin hybrid derivatives as promising leads to treat tuberculosis: Recent developments and critical aspects of structural design to exhibit anti-tubercular activity. Tuberculosis ,  2021, 127, 102050-0.
 [http://dx.doi.org/10.1016/j.tube.2020.102050] [PMID:  33540334]

[39]
Singh, A.; Yagnik, S.K.; Tripathi, N.; Khatoon, Y.; Pandey, M.; Verma, P. Design and synthesis of 3-arylcoumerin derivatives as a selective mao-B inhibitor. J. Pharm. Negat. Results,  2022, 31, 9820-9833.

[40]
Liu, L.; Chen, Y.; Zeng, R.F.; Liu, Y.; Xie, S.S.; Lan, J.S.; Ding, Y.; Yang, Y.T.; Yang, J.; Zhang, T. Design and synthesis of novel 3,4-dihydrocoumarins as potent and selective monoamine oxidase-B inhibitors with the neuroprotection against Parkinson’s disease. Bioorg. Chem.,  2021, 109, 104685-0.
 [http://dx.doi.org/10.1016/j.bioorg.2021.104685] [PMID:  33640631]

[41]
Li, F.; Li, D.; Liu, H.; Cao, B.B.; Jiang, F.; Chen, D.N.; Li, J.D. RNF216 regulates the migration of immortalized GnRH neurons by suppressing Beclin1-mediated autophagy. Front. Endocrinol.,  2019, 10, 12.
 [http://dx.doi.org/10.3389/fendo.2019.00012] [PMID:  30733708]

[42]
Shen, F.; Long, D.; Yu, T.; Chen, X.; Liao, Y.; Wu, Y.; Lin, X. Vinblastine differs from Taxol as it inhibits the malignant phenotypes of NSCLC cells by increasing the phosphorylation of Op18/stathmin. Oncol. Rep.,  2017, 37(4), 2481-2489.
 [http://dx.doi.org/10.3892/or.2017.5469] [PMID:  28259950]

[43]
Zhou, Y.; Li, Q.; Pan, R.; Wang, Q.; Zhu, X.; Yuan, C.; Cai, F.; Gao, Y.; Cui, Y. Regulatory roles of three miRNAs on allergen mRNA expression in Tyrophagus putrescentiae. Allergy,  2022, 77(2), 469-482.
 [http://dx.doi.org/10.1111/all.15111] [PMID:  34570913]

[44]
Enríquez, R.F.; Viña, D.; Uriarte, E.; Laguna, R.; Matos, M.J. 7‐Amidocoumarins as multitarget agents against neurodegenerative diseases: Substitution pattern modulation. ChemMedChem,  2021, 16(1), 179-186.
 [http://dx.doi.org/10.1002/cmdc.202000454] [PMID:  32700464]

[45]
Mellado, M.; Salas, C.O.; Uriarte, E.; Viña, D.; Gutiérrez, J.C.; Matos, M.J.; Cuellar, M. Design, synthesis and docking calculations of prenylated chalcones as selective monoamine oxidase B inhibitors with antioxidant activity. ChemistrySelect,  2019, 4(26), 7698-7703.
 [http://dx.doi.org/10.1002/slct.201901282]

[46]
Matos, M.J.; Pérez-Cruz, F.; Vazquez-Rodriguez, S.; Uriarte, E.; Santana, L.; Borges, F.; Olea-Azar, C. Remarkable antioxidant properties of a series of hydroxy-3-arylcoumarins. Bioorg. Med. Chem.,  2013, 21(13), 3900-3906. [l]
 [http://dx.doi.org/10.1016/j.bmc.2013.04.015] [PMID: 23673214]

[47]
Musa, M.A.; Badisa, V.L.D.; Aghimien, M.O.; Eyunni, S.V.K.; Latinwo, L.M. Identification of 7,8‐dihydroxy‐3‐phenylcoumarin as a reversible monoamine oxidase enzyme inhibitor. J. Biochem. Mol. Toxicol.,  2021, 35(2), e22651-e0.
 [http://dx.doi.org/10.1002/jbt.22651] [PMID:  33085988]

[48]
Zarmouh, N.O.; Eyunni, S.K.; Soliman, K.F.A. The benzopyrone biochanin-A as a reversible, competitive, and selective monoamine oxidase B inhibitor. BMC Complement. Altern. Med.,  2017, 17(1), 34.
 [http://dx.doi.org/10.1186/s12906-016-1525-y] [PMID:  28069007]

[49]
Musa, M.A.; Latinwo, L.M.; Joseph, M.Y.; Badisa, V.L. Identification of 7,8-diacetoxy-3-arylcoumarin derivative as a selective cytotoxic and apoptosis-inducing agent in a human prostate cancer cell line. Anticancer Res.,  2017, 37(11), 6005-6014.
 [PMID:  29061779]

[50]
McGann, M. OEDOCKING 3.0.1; OpenEye Scientific Software: Santa Fe, New Mexico, 0000.  

[51]
Lan, J.S.; Zhang, T.; Liu, Y.; Zhang, Y.; Hou, J.; Xie, S.S.; Yang, J.; Ding, Y.; Cai, Z. Synthesis and evaluation of small molecules bearing a benzyloxy substituent as novel and potent monoamine oxidase inhibitors. MedChemComm,  2017, 8(2), 471-478.
 [http://dx.doi.org/10.1039/C6MD00586A] [PMID:  30108765]

[52]
Rauhamäki, S.; Postila, P.A.; Niinivehmas, S.; Kortet, S.; Schildt, E.; Pasanen, M.; Manivannan, E.; Ahinko, M.; Koskimies, P.; Nyberg, N.; Huuskonen, P.; Multamäki, E.; Pasanen, M.; Juvonen, R.O.; Raunio, H.; Huuskonen, J.; Pentikäinen, O.T. Structure-activity relationship analysis of 3-phenylcoumarin-based monoamine oxidase B inhibitors. Front Chem.,  2018, 6, 4.
 [http://dx.doi.org/10.3389/fchem.2018.00041]

[53]
Wang, D.; Hong, R.Y.; Guo, M.; Liu, Y.; Chen, N.; Li, X.; Kong, D.X. Novel C7-substituted coumarins as selective monoamine oxidase inhibitors: Discovery, synthesis and theoretical simulation. Molecules,  2019, 24(21), 4003-0.
 [http://dx.doi.org/10.3390/molecules24214003] [PMID:  31694262]

[54]
Deng, Z.L.; Du, C.X.; Li, X.; Hu, B.; Kuang, Z.K.; Wang, R.; Feng, S.Y.; Zhang, H.Y.; Kong, D.X. Exploring the biologically relevant chemical space for drug discovery. J. Chem. Inf. Model.,  2013, 53(11), 2820-2828.
 [http://dx.doi.org/10.1021/ci400432a] [PMID:  24125686]

[55]
Hu, B.; Kuang, Z.K.; Feng, S.Y.; Wang, D.; He, S.B.; Kong, D.X. Three-dimensional biologically relevant spectrum (BRS-3D): Shape similarity profile based on PDB ligands as molecular descriptors. Molecules,  2016, 21(11), 1554.
 [http://dx.doi.org/10.3390/molecules21111554] [PMID:  27869685]

[56]
Jones, G.; Willett, P.; Glen, R.C.; Leach, A.R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking. J. Mol. Biol.,  1997, 267, 727-748.
 [http://dx.doi.org/10.1006/jmbi.1996.0897]

[57]
Matos, M.J.; Terán, C.; Castillo, P.Y.; Uriarte, E.; Santana, L.; Viña, D. Synthesis and study of a series of 3-arylcoumarins as potent and selective monoamine oxidase B inhibitors. J. Med. Chem.,  2011, 54(20), 7127-7137.
 [http://dx.doi.org/10.1021/jm200716y] [PMID:  21923181]

[58]
Yáñez, M.; Matías-Guiu, J.; Arranz-Tagarro, J.A.; Galán, L.; Viña, D.; Gómez-Pinedo, U.; Vela, Á.; Guerrero, A.; Vila, M.E.; García, A.G. The neuroprotection exerted by memantine, minocycline and lithium, against neurotoxicity of CSF from patients with amyotrophic lateral sclerosis, is antagonized by riluzole. Neurodegener. Dis.,  2014, 13(2-3), 171-179.
 [http://dx.doi.org/10.1159/000357281] [PMID:  24356417]

[59]
Schmidt, B.; Wolf, F.; Ehlert, C. Systematic investigation into the matsuda–heck reaction of α-methylene lactones: How conformational constraints direct the β-h-elimination step. J. Org. Chem.,  2016, 81(22), 11235-11249.
 [http://dx.doi.org/10.1021/acs.joc.6b02207] [PMID:  27750013]

[60]
Lan, J.S.; Xie, S.S.; Huang, M.; Hu, Y.J.; Kong, L.Y.; Wang, X.B. Chromanones: Selective and reversible monoamine oxidase B inhibitors with nanomolar potency. MedChemComm,  2015, 6(7), 1293-1302.
 [http://dx.doi.org/10.1039/C5MD00124B]

[61]
Xie, S.S.; Wang, X.; Jiang, N.; Yu, W.; Wang, K.D.G.; Lan, J.S.; Li, Z.R.; Kong, L.Y. Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer’s disease. Eur. J. Med. Chem.,  2015, 95, 153-165.
 [http://dx.doi.org/10.1016/j.ejmech.2015.03.040] [PMID:  25812965]

[62]
 Molinspiration chemoinformatics.  Available from:
          http://www.molinspiration.com/services/properties.html

[63]
Delogu, G.; Picciau, C.; Ferino, G.; Quezada, E.; Podda, G.; Uriarte, E.; Viña, D. Synthesis, human monoamine oxidase inhibitory activity and molecular docking studies of 3-heteroarylcoumarin derivatives. Eur. J. Med. Chem.,  2011, 46(4), 1147-1152.
 [http://dx.doi.org/10.1016/j.ejmech.2011.01.033] [PMID:  21316817]

[64]
Costas-Lago, M.C.; Besada, P.; Rodríguez-Enríquez, F.; Viña, D.; Vilar, S.; Uriarte, E.; Borges, F.; Terán, C. Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors. Eur. J. Med. Chem.,  2017, 139, 1-11.
 [http://dx.doi.org/10.1016/j.ejmech.2017.07.045] [PMID:  28797881]

[65]
Matos, M.J.; Vilar, S.; González-Franco, R.M.; Uriarte, E.; Santana, L.; Friedman, C.; Tatonetti, N.P.; Viña, D.; Fontenla, J.A. Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: Synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study. Eur. J. Med. Chem.,  2013, 63, 151-161.
 [http://dx.doi.org/10.1016/j.ejmech.2013.02.009] [PMID:  23474901]

[66]
Verdonk, M.L.; Cole, J.C.; Hartshorn, M.J.; Murray, C.W.; Taylor, R.D. Improved protein–ligand docking using GOLD. Proteins,  2003, 52(4), 609-623.
 [http://dx.doi.org/10.1002/prot.10465] [PMID:  12910460]

[67]
Rehuman, N.A.; Oh, J.M.; Nath, L.R.; Khames, A.; Abdelgawad, M.A.; Gambacorta, N.; Nicolotti, O.; Jat, R.K.; Kim, H.; Mathew, B. Halogenated coumarin-chalcones as multifunctional monoamine oxidase-B and butyrylcholinesterase inhibitors. ACS Omega,  2021, 6(42), 28182-28193.
 [http://dx.doi.org/10.1021/acsomega.1c04252] [PMID:  34723016]

[68]
Zhang, C.; Yang, K.; Yu, S.; Su, J.; Yuan, S.; Han, J.; Chen, Y.; Gu, J.; Zhou, T.; Bai, R.; Xie, Y. Design, synthesis and biological evaluation of hydroxypyridinone-coumarin hybrids as multimodal monoamine oxidase B inhibitors and iron chelates against Alzheimer’s disease. Eur. J. Med. Chem.,  2019, 180, 367-382.
 [http://dx.doi.org/10.1016/j.ejmech.2019.07.031] [PMID:  31325784]

[69]
Xie, Y.Y.; Lu, Z.; Kong, X.L.; Zhou, T.; Bansal, S.; Hider, R. Systematic comparison of the mono-, dimethyl- and trimethyl 3-hydroxy-4(1H)-pyridones – Attempted optimization of the orally active iron chelator, deferiprone. Eur. J. Med. Chem.,  2016, 115, 132-140.
 [http://dx.doi.org/10.1016/j.ejmech.2016.03.014] [PMID:  27014847]

[70]
Ma, Y.; Roy, S.; Kong, X.; Chen, Y.; Liu, D.; Hider, R.C. Design and synthesis of fluorinated iron chelators for metabolic study and brain uptake. J. Med. Chem.,  2012, 55(5), 2185-2195.
 [http://dx.doi.org/10.1021/jm201475u] [PMID:  22339047]

[71]
Binda, C.; Wang, J.; Pisani, L.; Caccia, C.; Carotti, A.; Salvati, P.; Edmondson, D.E.; Mattevi, A. Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: Safinamide and coumarin analogs. J. Med. Chem.,  2007, 50(23), 5848-5852.
 [http://dx.doi.org/10.1021/jm070677y] [PMID:  17915852]

[72]
Chen, Y.; Lin, H.; Zhu, J.; Gu, K.; Li, Q.; He, S.; Lu, X.; Tan, R.; Pei, Y.; Wu, L.; Bian, Y.; Sun, H. Design, synthesis, in vitro and in vivo evaluation of tacrine–cinnamic acid hybrids as multi-target acetyl- and butyrylcholinesterase inhibitors against Alzheimer’s disease. RSC Advances,  2017, 7(54), 33851-33867.
 [http://dx.doi.org/10.1039/C7RA04385F]

[73]
Rodríguez-Enríquez, F.; Viña, D.; Uriarte, E.; Fontenla, J.A.; Matos, M.J. Discovery and optimization of 3-thiophenylcoumarins as novel agents against Parkinson’s disease: Synthesis, in vitro and in vivo studies. Bioorg. Chem.,  2020, 101, 103986.
 [http://dx.doi.org/10.1016/j.bioorg.2020.103986] [PMID:  32569895]

[74]
Robinson, S.J.; Petzer, J.P.; Petzer, A.; Bergh, J.J.; Lourens, A.C. Selected furanochalcones as inhibitors of monoamine oxidase. Bioorg. Med. Chem. Lett.,  2013, 23(17), 4985-4989.
 [http://dx.doi.org/10.1016/j.bmcl.2013.06.050]

[75]
Duty, S.; Jenner, P. Animal models of Parkinson’s disease: A source of novel treatments and clues to the cause of the disease. Br. J. Pharmacol.,  2011, 164(4), 1357-1391.
 [http://dx.doi.org/10.1111/j.1476-5381.2011.01426.x] [PMID:  21486284]

[76]
Maria, FMB; Alexandra, M; Neves, G; Nuno, JDSPM; Francisco, OC Use of chromones, its derivatives, its pharmaceutically acceptable salts and its pro-drugs with the monoamine oxidase inhibiting activity and related therapeutic applications. PT Patent 104487B, 2012.

[77]
Alexandra, J; Duncan, GW; Ian, N; Jinto, JOSE Chitralekha, R Labelled coumarin derivatives.  WO Patent 2016097339A1, 2016.

[78]
Li, L.; Zhang, D.; Bao, X.; Gao, F.  Coumarin derivatives and application thereof in preventing and treating nervous system diseases. CN Patent 115246804A, 2022.

[79]
Liu, G.; Chen, N.; Sun, M.; Hu, J.; Song, X. Applications of coumarin derivatives in preventing and curing serious brain diseases. CN Patent 106588847A, 2019.

[80]
Liu, G.; Chen, N.; Sun, M.; Hu, J.; Song, X.  Preparation of coumarin derivative and application of coumarin derivative to control of serious cerebral disease. CN Patent 103450134A, 2017.

[81]
Sun, B. Synthesis method of C-3 alkyl substituted coumarin derivative. CN Patent 109761943B, 2021.

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DOI https://dx.doi.org/10.2174/0113895575290599240503080025	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607

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