Synthesis, Cytotoxic Evaluation, and Molecular Docking Studies of N-(7- hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide/benzamide Analogues

Author(s): Mohamed Jawed Ahsan*, Rupesh Kumar Kumawat, Surender Singh Jadav, Mohammed H. Geesi, Mohammed Afroz Bakht, Mohd. Zaheen Hassan, Abdulmalik Bin Saleh Al-Tamimi, Yassine Riadi, Salahuddin, Afzal Hussain, Narayan Murthy Ganta, Habibullah Khalilullah

Journal Name: Letters in Drug Design & Discovery

Volume 16 , Issue 2 , 2019

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Graphical Abstract:


Background: Cancer caused nearly 8.8 million deaths in 2015. Limited efficacy, selectivity, drug resistance and toxicity are major complications associated with chemotherapy, potentiating the discovery of anticancer agents.

Methods: A new series of N-(7-hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide/benzamide analogues (5a-j) was prepared from the precursor, 7-hydroxy-4-methyl-2H-chromen-2-one (3), as anticancer agent. The structural assignment of quinolone analogues (5a-j) was based on spectroscopic data analyses. The cytotoxicity was tested on breast cancer cell lines (MCF7 and MDA-MB- 231) by sulforhodamine B (SRB) assay and three dose-related parameters GI50, TGI, and LC50 were calculated.

Results: 2-(2-chlorophenoxy)-N-(7-hydroxy-4-methyl-2-oxoquinolin-1(2H)-yl)acetamide (5a) showed the most potent cytotoxicity against the MCF7 and MDA-MB-231 cancer cell lines with GI50 of 18.7 and 48.1 µM respectively. The glide scores of the compounds, 5a-d were found to be related to the cytotoxicity profile and the emodel scores for ligands, 5a-j were found to be related to significant cytotoxicity.

Conclusion: Compound 5a exhibited the most potent cytotoxicity and this report may provide some predictions to design more potent novel quinolines as cytotoxic agents.

Keywords: Anticancer agents, breast cancer cell lines, EGFR tyrosine kinase, SRB assay, quinolones.

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Year: 2019
Page: [182 - 193]
Pages: 12
DOI: 10.2174/1570180815666180501160047
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