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Synthesis, Characterization and Evaluation of Anticancer Activity of New Pyrazole-5-carboxamide Derivatives
Corresponding Author(s) : J. Prathyusha
Asian Journal of Chemistry,
Vol. 35 No. 8 (2023): Vol 35 Issue 8, 2023
Abstract
In recent years, pyrazole derivatives have emerged as a potentially game-changing new family of cancer chemotherapeutic drugs. Thus, present work used six distinct cancer cell lines to test the new pyrazole-5-carboxamide derivatives for the anticancer activity. Present study includes synthesis, characterization and the ligand-based molecular docking of the compounds. The process begins with ethyl 2,4-dioxopentanoate and methylhydrazine, which was cyclized to form ethyl 1,3-dimethyl-1H-pyrazole-5-carboxylate (2), which is then transformed to 1,3-dimethyl-1H-pyrazole-5-carbonyl chloride (3) through PCl3/I2. All the pyrazole-4-carboxamides (4a-n) were obtained by the acidic condensation of intermediate 3 with various substituted aryl amines (a-n). The antitumor activity against six cancer cell lines and one regular human cell line was measured using the MTT test. Two target proteins, human c-Met kinase and JAK1, were used in docking studies of the proposed compounds. When compared against the standard drug doxorubicin, most of the synthesized compounds (4a-n) showed the promising cytotoxicity profiles.
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References
Global Cancer Report-2018, International Agency for Research on Cancer, WHO report September (2021).
J.K. De Martino and D.L. Boger, Drugs Future, 33, 969 (2008); https://doi.org/10.1358/dof.2008.033.11.1247542
W.J. Curran, Oncology, 63, 29 (2002); https://doi.org/10.1159/000067145
K. Nurgali, R.T. Jagoe and R. Abalo, Front. Pharmacol., 9, 245 (2018); https://doi.org/10.3389/fphar.2018.00245
Y. Hu and J. Bajorath, J. Chem. Inf. Model., 51, 3138 (2011); https://doi.org/10.1021/ci200461w
M. Skoreñski and M. Sieñczyk, Pharmaceuticals, 14, 1164 (2021); https://doi.org/10.3390/ph14111164
G. Ion, O. Olaru, G. Nitulescu, I. Olaru, A. Tsatsakis, T. Burykina, D. Spandidos and G. Nitulescu, Oncol. Rep., 44, 589 (2020); https://doi.org/10.3892/or.2020.7636
R.F. Costa1, L.C. Turones, K.V.N. Cavalcante, I.A. Rosa Jr., C.H. Xavier, L.P. Rosseto, H.B. Napolitano, P.F. da Silva Castro, M.L. Ferreira-Neto, G.M. Galvão, R. Menegatti, G.R. Pedrino, E.A. Costa, J.L. Rodrigues-Martins and J.O. Fajemiroye, Front. Pharmacol., 12, 666725 (2021); https://doi.org/10.3389/fphar.2021.666725
M. Chalkha, M. Bakhouch, M. Akhazzane, M. Bourass, Y. Nicolas, G. Al Houari and M. El Yazidi, J. Chem. Sci., 132, 86 (2020); https://doi.org/10.1007/s12039-020-01792-3
A. Petrou, M. Fesatidou and A. Geronikaki, Molecules, 26, 3166 (2021); https://doi.org/10.3390/molecules26113166
H. Kumar, D. Saini, S. Jain and N. Jain, Eur. J. Med. Chem., 70, 248 (2013); https://doi.org/10.1016/j.ejmech.2013.10.004
M. Albratty and H. Alhazmi, Arab. J. Chem., 15, 103846 (2022); https://doi.org/10.1016/j.arabjc.2022.103846
E. Mohamed, N. Ismail, M. Hagras and H. Refaat, Future J. Pharm. Sci., 7, 1 (2021); https://doi.org/10.1186/s43094-020-00165-4
G. Nitulescu, Molecules, 27, 3300 (2022); https://doi.org/10.3390/molecules27103300
B. Poudyal and Bharghav, National J. Pharm. Sci., 1, 34 (2021).
P. Bose and S. Verstovsek, Hemasphere, 4, e424 (2020); https://doi.org/10.1097/HS9.0000000000000424
P. Cohen, D. Cross and P.A. Jänne, Nat. Rev. Drug Discov., 20, 551 (2021); https://doi.org/10.1038/s41573-021-00195-4
D. Kralj, M. Friedrich, U. Grošelj, S. Kiraly-Potpara, A. Meden, J. Wagger, G. Dahmann, B. Stanovnik and J. Svete, Tetrahedron, 65, 7151 (2009); https://doi.org/10.1016/j.tet.2009.06.021
M. Samet, R. Kasimogullari and S. Ok, J. Postdr. Res., 2, 64 (2014).
R. Ohno, A. Watanabe, T. Matsukawa, T. Ueda, H. Sakurai, M. Hori and K. Hirai, J. Pestic. Sci., 29, 15 (2004); https://doi.org/10.1584/jpestics.29.15
Z. Pourramezan, M. Oloomi and R. Kasra-Kermanshahi, Int. J. Prev. Med., 11, 132 (2020); https://doi.org/10.4103/ijpvm.IJPVM_307_19