Login Register Cart 0
Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Pyrazole Paradigms: Unveiling Synthetic Pathways and Unraveling Anti-Cancer Potential

Author(s): Poonam Kumari, Neetu Agrawal* and Somdutt Mujwar

Volume 20, Issue 8, 2024

Published on: 16 May, 2024

Page: [799 - 817] Pages: 19

DOI: 10.2174/0115734064312273240429110026

Price: $65

Abstract

This review investigates the synthetic methods and anti-cancer activities of pyrazole compounds. Various synthetic approaches, including traditional organic synthesis and microwaveassisted synthesis, have been used to change the pyrazole core structure, resulting in new compounds with improved pharmacological properties. The paper also covers the mechanisms of action that underpin pyrazole derivatives' anti-cancer characteristics, focusing on interactions with major molecular targets implicated in cancer growth and proliferation. SAR insights help to rationally develop novel anti-cancer drugs. In conclusion, the review emphasizes the versatility of pyrazole derivatives as scaffolds for the discovery and development of new anti-cancer medicines. By understanding synthesis routes and unravelling anti-cancer potential, this study hopes to encourage new research endeavours focused on leveraging the therapeutic advantages of pyrazole paradigms in the fight against cancer.

« Previous Next »
[1]
Udhayasurian, R.; Sivakumar, K. Facile NMI-MsCl mediated synthesis of novel pyrazole derivatives bearing heteroaryl amides as potent antimicrobial agents. ARKIVOC, 2022, 2022(5), 147-158.
[http://dx.doi.org/10.24820/ark.5550190.p011.756]
[2]
Alam, R.; Alam, M.A.; Panda, A.K.; Uddin, R. Design, synthesis and cytotoxicity evaluation of novel (E)-3-(3-aryl-1-phenyl-1 H -pyrazol-4-yl)-1-(pyridin-3-yl)prop-2-en-1-ones as anticancer agents. Heterocycl. Commun., 2016, 22(4), 221-225.
[http://dx.doi.org/10.1515/hc-2016-0042]
[3]
Zhang, Y.; Wu, C.; Zhang, N.; Fan, R.; Ye, Y.; Xu, J. Recent advances in the development of pyrazole derivatives as anticancer agents. Int. J. Mol. Sci., 2023, 24(16), 12724.
[http://dx.doi.org/10.3390/ijms241612724] [PMID: 37628906]
[4]
K, S.J.; Ganguly, S. A battle against aids: New pyrazole key to an older lock-reverse transcriptase. Int. J. Pharm. Pharm. Sci., 2016, 8(11), 75-79.
[http://dx.doi.org/10.22159/ijpps.2016v8i11.12634]
[5]
Bekhit, A.A.; Hassan, A.M.M.; Abd El Razik, H.A.; El-Miligy, M.M.M.; El-Agroudy, E.J.; Bekhit, A.E.D.A. New heterocyclic hybrids of pyrazole and its bioisosteres: Design, synthesis and biological evaluation as dual acting antimalarial-antileishmanial agents. Eur. J. Med. Chem., 2015, 94, 30-44.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.038] [PMID: 25768697]
[6]
Pathak, V.; Maurya, H.K.; Sharma, S.; Srivastava, K.K.; Gupta, A. Synthesis and biological evaluation of substituted 4,6-diarylpyrimidines and 3,5-diphenyl-4,5-dihydro-1H-pyrazoles as anti-tubercular agents. Bioorg. Med. Chem. Lett., 2014, 24(13), 2892-2896.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.094] [PMID: 24835631]
[7]
Ardiansah, B. Recent reports on pyrazole-based bioactive compounds as candidate for anticancer agents. Asian J. Pharm. Clin. Res., 2017, 10(12), 45.
[http://dx.doi.org/10.22159/ajpcr.2017.v10i12.22065]
[8]
Plem, S.C.; Müller, D.M.; Murguía, M.C. Key intermediates: A simple and highly selective synthesis of 5-Amino-1-Aryl-1H-Pyrazole-4-Carbonitriles for applications in the crop protection. Adv. Chem. Engineer. Sci., 2015, 5(3), 239-261.
[http://dx.doi.org/10.4236/aces.2015.53025]
[9]
Huang, X.F.; Lu, X.; Zhang, Y.; Song, G.Q.; He, Q.L.; Li, Q.S.; Yang, X.H.; Wei, Y.; Zhu, H.L. Synthesis, biological evaluation, and molecular docking studies of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives as novel anticancer agents. Bioorg. Med. Chem., 2012, 20(16), 4895-4900.
[http://dx.doi.org/10.1016/j.bmc.2012.06.056] [PMID: 22819191]
[10]
Luo, Y.; Zhang, S.; Qiu, K.M.; Liu, Z.J.; Yang, Y.S.; Fu, J.; Zhong, W.Q.; Zhu, H.L. Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors. Bioorg. Med. Chem. Lett., 2013, 23(4), 1091-1095.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.010] [PMID: 23312949]
[11]
Mansour, E.; Aboelnaga, A.; Nassar, E.M.; Elewa, S.I. A new series of thiazolyl pyrazoline derivatives linked to benzo[1,3]dioxole moiety: Synthesis and evaluation of antimicrobial and anti-proliferative activities. Synth. Commun., 2020, 50(3), 368-379.
[http://dx.doi.org/10.1080/00397911.2019.1695839]
[12]
Shamsuzzaman; Siddiqui, T.; Alam, M.G.; Dar, A.M. Synthesis, characterization and anticancer studies of new steroidal oxadiazole, pyrrole and pyrazole derivatives. J. Saudi Chem. Soc., 2015, 19(4), 387-391.
[http://dx.doi.org/10.1016/j.jscs.2012.04.009]
[13]
Zhu, S.L.; Wu, Y.; Liu, C.J.; Wei, C.Y.; Tao, J.C.; Liu, H.M. Design and stereoselective synthesis of novel isosteviol-fused pyrazolines and pyrazoles as potential anticancer agents. Eur. J. Med. Chem., 2013, 65, 70-82.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.044] [PMID: 23693151]
[14]
Abdelgawad, M.A.; Abdellatif, K.R.; Ahmed, O.M. Design, synthesis and anticancer screening of novel pyrazole derivatives linking to benzimidazole, benzoxazole and benzothiazole. Med. Chem., 2014, S1.
[15]
Abdelgawad, M.A.; Bakr, R.B.; Omar, H.A. Design, synthesis and biological evaluation of some novel benzothiazole/benzoxazole and/or benzimidazole derivatives incorporating a pyrazole scaffold as antiproliferative agents. Bioorg. Chem., 2017, 74, 82-90.
[http://dx.doi.org/10.1016/j.bioorg.2017.07.007] [PMID: 28772160]
[16]
Fahmy, H.H.; Srour, A.M.; Ismail, M.A.; Khater, M.A.; Serrya, R.A.; El-Manawaty, M.A. Design and synthesis of some new tri-substituted pyrazole derivatives as anticancer agents. Res. Chem. Intermed., 2016, 42(9), 6881-6892.
[http://dx.doi.org/10.1007/s11164-016-2502-2]
[17]
Kasiotis, K.M.; Tzanetou, E.N.; Stagos, D.; Fokialakis, N.; Koutsotheodorou, E.; Kouretas, D.; Haroutounian, S.A. Novel conformationally constrained pyrazole derivatives as potential anti-cancer agents. Zeitschrift fur Naturforsch. -. Sect. B. J. Chem. Sci., 2015, 70, 677-690.
[18]
Abdelrahman, M.; Ali, M. Synthesis of novel pyrazole derivatives bearing 1,2,4-triazole moiety as potential anticancer agents. Bull. Pharm. Sci., 2016, 39(1), 53-71.
[http://dx.doi.org/10.21608/bfsa.2016.62589]
[19]
Wang, F.Q.; Yang, H.; He, B.; Jia, Y.K.; Meng, S.Y.; Zhang, C.; Liu, H.M.; Liu, F.W. A novel domino approach for synthesis of indolyl tetrahydropyrano[4,3-c]pyrazole derivatives as anticancer agents. Tetrahedron, 2016, 72(38), 5769-5775.
[http://dx.doi.org/10.1016/j.tet.2016.07.078]
[20]
Wang, M.; Xu, S.; Lei, H.; Wang, C.; Xiao, Z.; Jia, S.; Zhi, J.; Zheng, P.; Zhu, W. Design, synthesis and antitumor activity of Novel Sorafenib derivatives bearing pyrazole scaffold. Bioorg. Med. Chem., 2017, 25(20), 5754-5763.
[http://dx.doi.org/10.1016/j.bmc.2017.09.003] [PMID: 28927801]
[21]
Rizk, S.A.; El-Sayed, A.A.; Mounier, M.M. Synthesis of novel pyrazole derivatives as antineoplastic agent. J. Heterocycl. Chem., 2017, 54(6), 3358-3371.
[http://dx.doi.org/10.1002/jhet.2956]
[22]
Mahal, A.; Wu, P.; Jiang, Z.H.; Wei, X. Synthesis and cytotoxic activity of novel tetrahydrocurcumin derivatives bearing pyrazole moiety. Nat. Prod. Bioprospect., 2017, 7(6), 461-469.
[http://dx.doi.org/10.1007/s13659-017-0143-9] [PMID: 29094265]
[23]
Dileep Kumar, A.; Bharath, S.; Dharmappa, R.N.; Naveen, S.; Lokanath, N.K.; Ajay Kumar, K. Design, synthesis and spectroscopic and crystallographic characterisation of novel functionalized pyrazole derivatives: biological evaluation for their cytotoxic, angiogenic and antioxidant activities. Res. Chem. Intermed., 2018, 44(9), 5635-5652.
[http://dx.doi.org/10.1007/s11164-018-3445-6]
[24]
Feng, J.; Qi, H.; Sun, X.; Feng, S.; Liu, Z.; Song, Y.; Qiao, X. Synthesis of novel pyrazole derivatives as promising dna-binding agents and evaluation of antitumor and antitopoisomerases I/II activities. Chem. Pharm. Bull., 2018, 66(11), 1065-1071.
[http://dx.doi.org/10.1248/cpb.c18-00546] [PMID: 30197406]
[25]
Behbehani, H.; Ibrahim, H.M. Synthetic strategy for pyrazolo[1,5- a]pyridine and Pyrido[1,2- b]indazole derivatives through AcOH and O 2 -promoted cross-dehydrogenative coupling reactions between 1,3-dicarbonyl compounds and N -Amino-2-iminopyridines. ACS Omega, 2019, 4(12), 15289-15303.
[http://dx.doi.org/10.1021/acsomega.9b02430] [PMID: 31552376]
[26]
Liu, D.C.; Gao, M.J.; Huo, Q.; Ma, T.; Wang, Y.; Wu, C.Z. Design, synthesis, and apoptosis-promoting effect evaluation of novel pyrazole with benzo[ d]thiazole derivatives containing aminoguanidine units. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 829-837.
[http://dx.doi.org/10.1080/14756366.2019.1591391] [PMID: 30915869]
[27]
Song, Y.; Feng, S.; Feng, J.; Dong, J.; Yang, K.; Liu, Z.; Qiao, X. Synthesis and biological evaluation of novel pyrazoline derivatives containing indole skeleton as anti-cancer agents targeting topoisomerase II. Eur. J. Med. Chem., 2020, 200, 112459.
[http://dx.doi.org/10.1016/j.ejmech.2020.112459] [PMID: 32502865]
[28]
Salih, S.M.; Alkubaisi, H.M.; Faraj, F.L. Synthesis and characterization of novel pyrazole derivatives from 4-florophenylhydrazine and study their cytotoxicity as anti-cancer agent 11. Egypt. J. Chem., 2021, 64.
[29]
Yamali, C.; Gul, H.I.; Ece, A.; Bua, S.; Angeli, A.; Sakagami, H.; Sahin, E.; Supuran, C.T. Synthesis, biological evaluation and in silico modelling studies of 1,3,5-trisubstituted pyrazoles carrying benzenesulfonamide as potential anticancer agents and selective cancer-associated hCA IX isoenzyme inhibitors. Bioorg. Chem., 2019, 92, 103222.
[http://dx.doi.org/10.1016/j.bioorg.2019.103222] [PMID: 31499260]
[30]
Anwar, M.M.; Abd El-Karim, S.S.; Mahmoud, A.H.; Amr, A.E.G.E.; Al-Omar, M.A. A comparative study of the anticancer activity and PARP-1 inhibiting effect of benzofuran–pyrazole scaffold and its nano-sized particles in human breast cancer cells. Molecules, 2019, 24(13), 2413.
[http://dx.doi.org/10.3390/molecules24132413] [PMID: 31261939]
[31]
Doan, N.Q.H.; Nguyen, N.T.K.; Duong, V.B.; Nguyen, H.T.T.; Vong, L.B.; Duong, D.N.; Nguyen, N.T.T.; Nguyen, T.L.T.; Do, T.T.H.; Truong, T.N. Synthesis, biological evaluation, and molecular modeling studies of 1-Aryl-1 H -pyrazole-fused curcumin analogues as anticancer agents. ACS Omega, 2022, 7(38), 33963-33984.
[http://dx.doi.org/10.1021/acsomega.2c02933] [PMID: 36188331]
[32]
Matiychuk, V.S.; Potopnyk, M.A.; Obushak, M.D. A simple and efficient synthesis of ethyl 1‐Aryl‐4‐formyl‐1 H ‐pyrazole‐3‐carboxylates. J. Heterocycl. Chem., 2013, 50(S1), E43-E47.
[http://dx.doi.org/10.1002/jhet.1042]
[33]
Joshi, G.; Sharma, M.; Kalra, S.; Gavande, N.S.; Singh, S.; Kumar, R. Design, synthesis, biological evaluation of 3,5-diaryl-4,5-dihydro-1H-pyrazole carbaldehydes as non-purine xanthine oxidase inhibitors: Tracing the anticancer mechanism via xanthine oxidase inhibition. Bioorg. Chem., 2021, 107, 104620.
[http://dx.doi.org/10.1016/j.bioorg.2020.104620] [PMID: 33454509]
[34]
Sun, J.; Lv, X.H.; Qiu, H.Y.; Wang, Y.T.; Du, Q.R.; Li, D.D.; Yang, Y.H.; Zhu, H.L. Synthesis, biological evaluation and molecular docking studies of pyrazole derivatives coupling with a thiourea moiety as novel CDKs inhibitors. Eur. J. Med. Chem., 2013, 68, 1-9.
[http://dx.doi.org/10.1016/j.ejmech.2013.07.003] [PMID: 23933045]
[35]
Abd El-Karim, S.S.; Anwar, M.M.; Mohamed, N.A.; Nasr, T.; Elseginy, S.A. Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran–pyrazole derivatives as anticancer agents. Bioorg. Chem., 2015, 63, 1-12.
[http://dx.doi.org/10.1016/j.bioorg.2015.08.006] [PMID: 26368040]
[36]
Fahmy, H.; Khalifa, N.; Ismail, M.; El-Sahrawy, H.; Nossier, E. Biological validation of novel polysubstituted pyrazole candidates with in vitro anticancer activities. Molecules, 2016, 21(3), 271.
[http://dx.doi.org/10.3390/molecules21030271] [PMID: 26927048]
[37]
Dawood, K.M.; Eldebss, T.M.A.; El-Zahabi, H.S.A.; Yousef, M.H.; 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, 740-749.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.042] [PMID: 24231309]
[38]
Li, X.; Lu, X.; Xing, M.; Yang, X.H.; Zhao, T.T.; Gong, H.B.; Zhu, H.L. Synthesis, biological evaluation, and molecular docking studies of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives as anticancer agents. Bioorg. Med. Chem. Lett., 2012, 22(11), 3589-3593.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.066] [PMID: 22572580]
[39]
Nitulescu, G.; Draghici, C.; Olaru, O. New potential antitumor pyrazole derivatives: Synthesis and cytotoxic evaluation. Int. J. Mol. Sci., 2013, 14(11), 21805-21818.
[http://dx.doi.org/10.3390/ijms141121805] [PMID: 24192822]
[40]
Nitulescu, G.M.; Draghici, C.; Olaru, O.T.; Matei, L.; Ioana, A.; Dragu, L.D.; Bleotu, C. Synthesis and apoptotic activity of new pyrazole derivatives in cancer cell lines. Bioorg. Med. Chem., 2015, 23(17), 5799-5808.
[http://dx.doi.org/10.1016/j.bmc.2015.07.010] [PMID: 26193760]
[41]
Yadlapalli, R.K.; Chourasia, O.P.; Vemuri, K.; Sritharan, M.; Perali, R.S. Synthesis and in vitro anticancer and antitubercular activity of diarylpyrazole ligated dihydropyrimidines possessing lipophilic carbamoyl group. Bioorg. Med. Chem. Lett., 2012, 22(8), 2708-2711.
[http://dx.doi.org/10.1016/j.bmcl.2012.02.101] [PMID: 22437116]
[42]
Zhang, W.M.; Xing, M.; Zhao, T.T.; Ren, Y.J.; Yang, X.H.; Yang, Y.S.; Lv, P.C.; Zhu, H.L. Synthesis, molecular modeling and biological evaluation of cinnamic acid derivatives with pyrazole moieties as novel anticancer agents. RSC Advances, 2014, 4(70), 37197-37207.
[http://dx.doi.org/10.1039/C4RA05257A]
[43]
Belal, A. Abdelgawad, M.A. New benzothiazole/benzoxazole-pyrazole hybrids with potential as COX inhibitors: Design, synthesis and anticancer activity evaluation. Res. Chem. Intermed., 2017, 43(7), 3859-3872.
[http://dx.doi.org/10.1007/s11164-016-2851-x]
[44]
Alam, R.; Wahi, D.; Singh, R.; Sinha, D.; Tandon, V.; Grover, A. Rahisuddin, Design, synthesis, cytotoxicity, HuTopoIIα inhibitory activity and molecular docking studies of pyrazole derivatives as potential anticancer agents. Bioorg. Chem., 2016, 69, 77-90.
[http://dx.doi.org/10.1016/j.bioorg.2016.10.001] [PMID: 27744115]
[45]
Ganga Reddy, V.; Srinivasa Reddy, T.; Lakshma Nayak, V.; Prasad, B.; Reddy, A.P.; Ravikumar, A.; Taj, S.; Kamal, A. Design, synthesis and biological evaluation of N -((1-benzyl-1 H -1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1 H -pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors. Eur. J. Med. Chem., 2016, 122, 164-177.
[http://dx.doi.org/10.1016/j.ejmech.2016.06.011] [PMID: 27344493]
[46]
Kaur, G.; Cholia, R.P.; Joshi, G.; Amrutkar, S.M.; Kalra, S.; Mantha, A.K.; Banerjee, U.C.; Kumar, R. Anticancer activity of dihydropyrazolo[1,5‐ c]quinazolines against rat C6 glioma cells via inhibition of topoisomerase II. Arch. Pharm., 2018, 351(6), 1800023.
[http://dx.doi.org/10.1002/ardp.201800023] [PMID: 29737542]
[47]
Maciejewska, N.; Olszewski, M.; Jurasz, J.; Serocki, M.; Dzierzynska, M.; Cekala, K.; Wieczerzak, E.; Baginski, M. Novel chalcone-derived pyrazoles as potential therapeutic agents for the treatment of non-small cell lung cancer. Sci. Rep., 2022, 12(1), 3703.
[http://dx.doi.org/10.1038/s41598-022-07691-6] [PMID: 35260633]
[48]
Ahmed, M.F.; Santali, E.Y.; El-Haggar, R. Novel piperazine–chalcone hybrids and related pyrazoline analogues targeting VEGFR-2 kinase; design, synthesis, molecular docking studies, and anticancer evaluation. J. Enzyme Inhib. Med. Chem., 2021, 36(1), 308-319.
[http://dx.doi.org/10.1080/14756366.2020.1861606] [PMID: 33349069]
[49]
Nossier, E.; Abd El-Karim, S.; Khalifa, N.; El-Sayed, A.; Hassan, E.; El-Hallouty, S. Kinase inhibitory activities and molecular docking of a novel series of anticancer pyrazole derivatives. Molecules, 2018, 23(12), 3074.
[http://dx.doi.org/10.3390/molecules23123074] [PMID: 30477238]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy