Copyright (c) 2024 Jyothi Kasapogu
This work is licensed under a Creative Commons Attribution 4.0 International License.
Novel Pyrimidine Tethered Benzamide Derivatives as Potential Anticancer Agents: Synthesis, Characterization, Molecular Docking and In vitro Cytotoxicity Evaluation
Corresponding Author(s) : K. Jyothi
Asian Journal of Chemistry,
Vol. 36 No. 12 (2024): Vol 36 Issue 12, 2024
Abstract
Current research work presents the synthesis, characterization, molecular docking study and in vitro cytotoxicity evaluation of novel pyrimidine-tethered benzamide derivatives as potential anticancer agents. The synthesis involved multi-steps procedure, including the synthesis of various chalcones (3a-t) with corresponding ketones (1 and 2) and substituted aldehydes (a-j), followed by pyrimidine amines (5a-t) with condensation of chalcones and guanidine and finally pyrimidinyl benzamide derivatives (8a-t) from compounds 5a-t coupling with acid chloride (7) using DIBAL-H. Synthesized compounds characterized by NMR spectroscopy and HRMS. The molecular docking studies were conducted against EGFR (6LUD) and CDK-4 (7SJ3) receptors, revealing distinct binding affinities influenced by substituent groups. Additionally, the cytotoxicity of the synthesized compounds was evaluated using the MTT assay against various cancer cell lines, including A-549 (non-small cell lung cancer), HCT-116 (colorectal cancer), PANC-1 (pancreatic cancer) and HaLa (cervical cancer), along with one normal human embryonic kidney cell line (HEK-293). Among the synthesized compounds, derivatives 8f and 8j exhibited the best anticancer activity against A-549 cells, compounds 8j and 8e showed exceptional potency against HCT-116 cells, compounds 8f and 8j demonstrated high efficacy against PANC-1 cells and compound 8h displayed remarkable potency against HaLa cells. The findings highlight the potential of these pyrimidinyl benzamide derivatives as targeted anticancer agents.
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S.M. El-Messery, G.S. Hassan, M.N. Nagi, E.E. Habib, S.T. Al-Rashood and H.I. El-Subbagh, Bioorg. Med. Chem. Lett., 26, 4815 (2016); https://doi.org/10.1016/j.bmcl.2016.08.022
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T.V. Sreevidya, B. Narayana and H.S. Yathirajan, Cent. Eur. J. Chem., 8, 174 (2010); https://doi.org/10.2478/s11532-009-0124-x
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J.A. Greenberg and T. Sammakia, J. Org. Chem., 82, 3245 (2017); https://doi.org/10.1021/acs.joc.6b02931
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