Ravi K. Mittal and Priyank Purohit* Pages 1981 - 1991 ( 11 )
Background: The quinoline scaffold has been an attraction due to its pharmacological activities such as anti-HIV, anti-neoplastic, anti-asthmatic, anti-tuberculotic, anti-fungal, and anti-bacterial.Objective: The designed quinoline-3-carboxylate derivatives were synthesized through a two-step reaction and evaluated for antiproliferative activity against MCF-7 and K562 cell lines. Methods: Synthesized compounds were characterized by modern analytical techniques like NMR, 2DNMR, mass, and IR. Moreover, the purity of compounds was analyzed through the HPLC. In the progress of biological results, all synthesized compounds were evaluated for antiproliferative activity against MCF-7 and K562 cell lines. Results: The synthesized compounds exhibited micromolar inhibition in all over the ranges, however, some of the compounds showed better activity than the standard anticancer drug such, as 4m and 4n with the IC50 value of 0.33μM against the MCF-7 cell line, and the compounds 4k and 4m showed potential activity against the K562 cell line with the IC50 value of 0.28μM. The anti-cancer activities of compounds were found to be through the up-regulation of intrinsic apoptosis pathways. Conclusion: The biological data of all compounds in both cell lines were utilized for the structural activity relationship of the quinoline-3-carboxylate pharmacophore. The active lead was further validated through rigorous in silico studies for the drug-likeness (QED) and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties. Here in the present research is utilized for the demonstration of an important pharmacophore, which could be utilized for further development to become a lead as an anticancer agent with minimal toxicity.
Cancer, activity, drug discovery, in silico, cell line, antiproliferative agent.
Department of Natural Product, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar, Punjab-160062, Department of Pharmacy, HIMT, Gautam Budh Nagar, Greater Noida, Uttar Pradesh, 201308