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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review

Author(s): Subham Das, Saleem Akbar, Bahar Ahmed, Rikeshwar Prasad Dewangan, Mohammad Kashif Iqubal, Ashif Iqubal, Pooja Chawla, Faheem Hyder Pottoo* and Alex Joseph*

Volume 21, Issue 10, 2022

Published on: 02 June, 2021

Page: [940 - 951] Pages: 12

DOI: 10.2174/1871527320666210602152308

Price: $65

Abstract

As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact in chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task in both the past and present. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is discovering novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in μM), recent patents, and a brief history as neuroprotective agents.

Keywords: Pyrazole, heteroaromatic ring, neurological disorder, neuroprotective agents, structural-activity relationship, heterocycles.

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[1]
Grewal AS, Sharma SK, Pandita D, Lather V. Synthesis, docking and evaluation of novel pyrazole carboxamide derivatives as multifunctional anti-alzheimer’s agents. J Med Chem Toxicol 2017; 2(1): 47-54.
[2]
Ju Y, Varma RS. Aqueous N-heterocyclization of primary amines and hydrazines with dihalides: microwave-assisted syntheses of N-azacycloalkanes, isoindole, pyrazole, pyrazolidine, and phthalazine derivatives. J Org Chem 2006; 71(1): 135-41.
[http://dx.doi.org/10.1021/jo051878h] [PMID: 16388628]
[3]
Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 2007; 6(11): 881-90.
[http://dx.doi.org/10.1038/nrd2445] [PMID: 17971784]
[4]
Li X, He L, Chen H, Wu W, Jiang H. Copper-catalyzed aerobic C(sp2)-H functionalization for C-N bond formation: synthesis of pyrazoles and indazoles. J Org Chem 2013; 78(8): 3636-46.
[http://dx.doi.org/10.1021/jo400162d] [PMID: 23547954]
[5]
Küçükgüzel ŞG, Şenkardeş S. Recent advances in bioactive pyrazoles. Eur J Med Chem 2015; 97(1): 786-815.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.059] [PMID: 25555743]
[6]
Kumar V, Kaur K, Gupta GK, Sharma AK. Pyrazole containing natural products: Synthetic preview and biological significance. Eur J Med Chem 2013; 69: 735-53.
[http://dx.doi.org/10.1016/j.ejmech.2013.08.053] [PMID: 24099993]
[7]
Li M, Zhao BX. Progress of the synthesis of condensed pyrazole derivatives (from 2010 to mid-2013). Eur J Med Chem 2014; 85: 311-40.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.102] [PMID: 25104650]
[8]
Kumar H, Saini D, Jain S, Jain N. Pyrazole scaffold: A remarkable tool in the development of anticancer agents. Eur J Med Chem 2013; 70: 248-58.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.004] [PMID: 24161702]
[9]
B’Bhatt H, Sharma S. Synthesis and antimicrobial activity of pyrazole nucleus containing 2-thioxothiazolidin-4-one derivatives. Arab J Chem 2017; 10: S1590-6.
[http://dx.doi.org/10.1016/j.arabjc.2013.05.029]
[10]
Abdel-Aziz M, Abuo-Rahma Gel-D, Hassan AA. Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities. Eur J Med Chem 2009; 44(9): 3480-7.
[http://dx.doi.org/10.1016/j.ejmech.2009.01.032] [PMID: 19268406]
[11]
Malladi S, Isloor AM, Peethambar SK, Ganesh BM, Goud PSK. Synthesis and antimicrobial activity of some new pyrazole containing cyanopyridone derivatives. Der Pharma Chem 2012; 4(1): 43-52.
[12]
Kaushik D, Khan SA, Chawla G, Kumar S. N′-[(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene] 2/4-substituted hydrazides: Synthesis and anticonvulsant activity. Eur J Med Chem 2010; 45(9): 3943-9.
[http://dx.doi.org/10.1016/j.ejmech.2010.05.049] [PMID: 20573423]
[13]
Koca I, Özgür A, Coşkun KA, Tutar Y. Synthesis and anticancer activity of acyl thioureas bearing pyrazole moiety. Bioorganic Med Chem 2013; 21(13): 3859-65.
[14]
Dawood KM, Eldebss TMA, El-Zahabi HSA, Yousef MH, Metz P. Synthesis of some new pyrazole-based 1,3-thiazoles and 1,3,4-thiadiazoles as anticancer agents. Eur J Med Chem 2013; 70: 740-9.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.042] [PMID: 24231309]
[15]
Daidone G, Maggio B, Raffa D, et al. Synthesis and Pharmacological Study of Ethyl 1-Methyl-5-[2-Substituted-4-Oxo-3(4H)-Quinazolinyl]-1H-Pyrazole-4-Acetates. Eur J Med Chem 1994; 29(9): 707-11.
[http://dx.doi.org/10.1016/0223-5234(94)90033-7]
[16]
Vijesh AM, Isloor AM, Shetty P, Sundershan S, Fun HK. New pyrazole derivatives containing 1,2,4-triazoles and benzoxazoles as potent antimicrobial and analgesic agents. Eur J Med Chem 2013; 62: 410-5.
[http://dx.doi.org/10.1016/j.ejmech.2012.12.057] [PMID: 23385092]
[17]
Gökhan-Kelekçi N, Yabanoǧlu S, Küpeli E, et al. Therapeutic approach in alzheimer disease: Some novel pyrazole derivatives as dual mao-b inhibitors and antiinflammatory analgesics. Bioorganic Med Chem 2007; 15(17): 5775-86.
[18]
Khunt RC, Khedkar VM, Chawda RS, Chauhan NA, Parikh AR, Coutinho EC. Synthesis, antitubercular evaluation and 3d-qsar study of n-phenyl-3-(4-fluorophenyl)-4-substituted pyrazole derivatives. Bioorganic Med Chem Lett 2012; 22(1): 666-78.
[19]
Pathak RB, Chovatia PT, Parekh HH. Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives. Bioorganic Med Chem Lett 2012; 22(15): 5129-33.
[20]
Raffa D, Maggio B, Raimondi MV, et al. Recent advanced in bioactive systems containing pyrazole fused with a five membered heterocycle. Eur J Med Chem 2015; 97(1): 732-46.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.023] [PMID: 25549911]
[21]
Bertram L, Tanzi RE. The genetic epidemiology of neurodegenerative disease. J Clin Invest 2005; 115(6): 1449-57.
[http://dx.doi.org/10.1172/JCI24761] [PMID: 15931380]
[22]
Mir RH, Sawhney G, Pottoo FH, et al. Role of environmental pollutants in Alzheimer’s disease: A review. Environ Sci Pollut Res Int 2020; 27(36): 44724-42.
[http://dx.doi.org/10.1007/s11356-020-09964-x] [PMID: 32715424]
[23]
Ibrahim AM, Pottoo FH, Dahiya ES, Khan FA, Kumar JBS. Neuron-glia interactions: Molecular basis of Alzheimer’s disease and applications of neuroproteomics. Eur J Neurosci 2020; 52(2): 2931-43.
[http://dx.doi.org/10.1111/ejn.14838] [PMID: 32463535]
[24]
Nigar S, Pottoo F, Tabassum N, Verma S, Javed M. Molecular insights into the role of inflammation and oxidative stress in epilepsy. J Adv Med Pharm Sci 2016; 10(1): 1-9.
[http://dx.doi.org/10.9734/JAMPS/2016/24441]
[25]
Sharma P, Sharma A, Fayaz F, Wakode S, Pottoo FH. Biological signatures of Alzheimer’s disease. Curr Top Med Chem 2020; 20(9): 770-81.
[http://dx.doi.org/10.2174/1568026620666200228095553] [PMID: 32108008]
[26]
Mir RH, Shah AJ. Natural anti-inflammatory compounds as drug candidates in Alzheimer’s disease. Molecules 2018; 23(1):134.
[27]
Ahmad MA, Pottoo FH, Akbar M. Gene therapy repairs for the epileptic brain: potential for treatment and future directions. Curr Gene Ther 2020; 19(6): 367-75.
[http://dx.doi.org/10.2174/1566523220666200131142423] [PMID: 32003688]
[28]
Shafi S, Singh A, Gupta P, et al. Deciphering the role of aberrant protein post translational modification in the pathology of neurodegeneration. CNS Neurol Disord Drug Targets 2021; 20(1): 54-67.
[http://dx.doi.org/10.2174/1871527319666200903162200]
[29]
Iqubal A, Rahman SO, Ahmed M, et al. Current quest in natural bioactive compounds for Alzheimer’s disease: Multi-targeted-designed-ligand based approach with preclinical and clinical based evidence. Curr Drug Targets 2021; 22(6): 685-720.
[30]
Goswami S, Kareem O, Goyal RK, et al. Role of forkhead transcription factors of the o class (foxo) in development and progression of Alzheimer’s disease. CNS Neurol Disord Drug Targets 2020; 19(9): 709-21.
[http://dx.doi.org/10.2174/1871527319666201001105553] [PMID: 33001019]
[31]
Stein DG. Brain injury: Functional recovery after. Elsevier 2016.
[32]
Tamborini L, Pinto A, Mastronardi F, et al. 3-Carboxy-pyrazolinalanine as a new scaffold for developing potent and selective NMDA receptor antagonists. Eur J Med Chem 2013; 68: 33-7.
[http://dx.doi.org/10.1016/j.ejmech.2013.07.010] [PMID: 23954238]
[33]
Mohareb RM, Ahmed HH, Elmegeed GA, Abd-Elhalim MM, Shafic RW. Development of new indole-derived neuroprotective agents. Bioorganic Med Chem 2011; 19(9): 2966-74.
[34]
Ahsan MJ. Anticonvulsant activity and neuroprotection assay of 3-substituted-n-aryl-6,7-dimethoxy-3a,4-dihydro-3hindeno[1,2-c]pyrazole-2-carboxamide analogues. Arab J Chem 2013; 3-7.
[35]
Das S, Anu KR, Birangal SR, et al. Role of comorbidities like diabetes on severe acute respiratory syndrome coronavirus-2: A review. Life Sci. 2020; 258: 118202.
[36]
Manoj A, Das S, Kunnath Ramachandran A, Alex AT, Joseph A. SGLT2 inhibitors, an accomplished development in field of medicinal chemistry: An extensive review. Future Med Chem 2020; 12(21): 1961-1990.
[37]
Anu KR, Das S, Joseph A, Shenoy GG, Alex AT, Mudgal J. Neurodegenerative pathways in Alzheimer’s disease: A review. Curr Neuropharmacol 2021; 19(5): 679-692.
[38]
Anu KR, Das S, Joseph A. Crosstalk between covid-19 and associated neurological disorders: A review. Curr Neuropharmacol 2021; 19(10): 1688-1700.
[39]
Allec SI, Sun Y, Sun J, Chang CA, Wong BM. Heterogeneous CPU+GPU-enabled simulations for DFTB molecular dynamics of large chemical and biological systems. J Chem Theory Comput 2019; 15(5): 2807-15.
[http://dx.doi.org/10.1021/acs.jctc.8b01239] [PMID: 30916958]
[40]
Bhattacharya S, Asati V, Mishra M, Das R, Kashaw V, Kashaw SK. Integrated computational approach on sodium-glucose co-transporter 2 (SGLT2) inhibitors for the development of novel antidiabetic agents. J Mol Struct 2021; 1227: 129511.
[http://dx.doi.org/10.1016/j.molstruc.2020.129511]
[41]
Ansari A, Ali A, Asif M. Shamsuzzaman. review: Biologically active pyrazole derivatives. New J Chem 2016; 41(1): 16-41.
[http://dx.doi.org/10.1039/C6NJ03181A]
[42]
Faisal M, Saeed A, Hussain S, Dar P, Larik FA. Recent developments in synthetic chemistry and biological activities of pyrazole derivatives. J Chem Sci 2019; 131(8): 1-30.
[http://dx.doi.org/10.1007/s12039-019-1646-1]
[43]
Khan MF, Alam MM, Verma G, Akhtar W, Akhter M, Shaquiquzzaman M. The therapeutic voyage of pyrazole and its analogs: A review. Eur J Med Chem 2016; 120: 170-201.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.077] [PMID: 27191614]
[44]
Karrouchi K, Radi S, Ramli Y, et al. Synthesis and pharmacological activities of pyrazole derivatives: A review Molecules 2018; 23(1):134.
[http://dx.doi.org/10.3390/molecules23010134]
[45]
Duffy L A. Pyrazole derivatives as P38 map inhibitors. 2016. US009249125B2
[46]
Mitchell L H, Shapiro G, Chesworth R, Boriark-Sjodin P A, Oscar Miguel M. Pyrazole derivatives as PRMT1 inhibitors and uses thereof. US 20160039767A1, 2016.
[47]
Gabr M, Murugan NA. Discovery of biphenyl pyrazole scaffold for neurodegenerative diseases: A novel class of acetylcholinesterase-centered multitargeted ligands. Bioorg Med Chem Lett 2020; 30(17): 127370.
[http://dx.doi.org/10.1016/j.bmcl.2020.127370] [PMID: 32738978]
[48]
Mishra S, Patel S, Halpani CG. Recent updates in curcumin pyrazole and isoxazole derivatives: Synthesis and biological application. Chem Biodivers 2019; 16(2): e1800366.
[http://dx.doi.org/10.1002/cbdv.201800366] [PMID: 30460748]
[49]
Khoobi M, Ghanoni F, Nadri H, et al. New tetracyclic tacrine analogs containing pyrano[2,3-c]pyrazole: efficient synthesis, biological assessment and docking simulation study. Eur J Med Chem 2015; 89: 296-303.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.049] [PMID: 25462245]
[50]
Liao L, Shi J, Jiang C, et al. Activation of anti-oxidant of curcumin pyrazole derivatives through preservation of mitochondria function and Nrf2 signaling pathway. Neurochem Int 2019; 125: 82-90.
[http://dx.doi.org/10.1016/j.neuint.2019.01.026] [PMID: 30771374]
[51]
Saleh TM, Saleh MC, Connell BJ, Kucukkaya I, Abd-El-Aziz AS. A novel synthetic chemical entity (UPEI-800) is neuroprotective in vitro and in an in vivo rat model of oxidative stress. Clin Exp Pharmacol Physiol 2017; 44(10): 993-1000.
[http://dx.doi.org/10.1111/1440-1681.12785] [PMID: 28504843]
[52]
Taslimi P, Türkan F, Cetin A, et al. Pyrazole[3,4-d]pyridazine derivatives: Molecular docking and explore of acetylcholinesterase and carbonic anhydrase enzymes inhibitors as anticholinergics potentials. Bioorg Chem 2019; 92: 103213.
[http://dx.doi.org/10.1016/j.bioorg.2019.103213] [PMID: 31470200]
[53]
Turkan F, Cetin A, Taslimi P, Karaman M, Gulçin İ. Synthesis, biological evaluation and molecular docking of novel pyrazole derivatives as potent carbonic anhydrase and acetylcholinesterase inhibitors. Bioorg Chem 2019; 86(86): 420-7.
[http://dx.doi.org/10.1016/j.bioorg.2019.02.013] [PMID: 30769267]
[54]
Azimi F, Ghasemi JB, Azizian H, et al. Design and synthesis of novel pyrazole-phenyl semicarbazone derivatives as potential α-glucosidase inhibitor: Kinetics and molecular dynamics simulation study. Int J Biol Macromol 2021; 166: 1082-95.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.10.263] [PMID: 33157144]
[55]
Ucar A, Ozmen Ozgun D, Alak G, et al. Biological activities of a newly synthesized pyrazoline derivative 4-(3-(4-bromophenyl)-5-(2,4-dimethoxyphenyl)-4,5-dihydro-1h-pyrazol-1-yl) benzenesulfonamide (b4) compound on rainbow trout alevins, oncorhynchus mykiss. Vitr Cell Dev Biol - Anim 2021; 57: 17-20.
[56]
Zaiter J, Hibot A, Hafid A, et al. Evaluation of the cellular protection by novel spiropyrazole compounds in dopaminergic cell death. Eur J Med Chem 2021; 213: 113140.
[http://dx.doi.org/10.1016/j.ejmech.2020.113140] [PMID: 33454549]

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