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

[ Vol. 16 , Issue. 2 ]

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 and Habibullah Khalilullah   Pages 182 - 193 ( 12 )

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.

Affiliation:

Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62529, Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Ambabari Circle, Jaipur, Rajasthan 302 039, Department of Pharmaceutical Science & Technology, Birla Institute of Science & Technology, Mesra, Ranchi, Jharkhand 835 215, Department of Chemistry, College of Science & Humanities, Prince Sattam Bin Abdulaziz University, P.O. Box 11323, Department of Chemistry, College of Science & Humanities, Prince Sattam Bin Abdulaziz University, P.O. Box 11323, Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 62529, Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, P.O. Box 11323, Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdul Aziz University, P.O. Box 11323, Department of Pharmaceutical Chemistry, Noida Institute of Technology (Pharmacy Institute), Knowledge Park-2, Greater Noida, Uttar Pradesh 201 306, Department of Pharmaceutical Science & Technology, Birla Institute of Science & Technology, Mesra, Ranchi, Jharkhand 835 215, Department of Pharmaceutical Chemistry, Vishnu Institute of Pharmaceutical Sciences, Narsapur 502 313, Department of Pharmaceutical Chemistry, Unaizah College of Pharmacy, Qassim University, Al-Qassim 51911

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