Design and Synthesis of Some New N-(Thiazol-2-yl) Benzamides of Quinoxaline as DNA Topoisomerase II Targeting Anticancer Agents and ADMET

Abstract

We herein, described the synthesis of some new N-(thiazol-2-yl)benzamides of quinoxaline. All the synthesized compounds were evaluated for their in vitro anticancer activity against three human cancer cell lines including MCF-7 (breast cancer), A549 (lung cancer) and HepG2 (liver cancer). In this study, etoposide was used as a positive control. The results revealed that the compounds 6d, 6e, 6i, 6j and 6m exhibited promising activity against three cancer cell lines. Predominantly, compound 6i displayed greater activity than the standard drug etoposide on MCF-7, A549 and HepG2 with IC₅₀ values of 0.95 ± 0.063, 1.32 ± 0.16 and 1.24 ± 0.10 µM respectively. The cell viability assay carried out toward a normal breast cell line (MCF-10A) for five potent compounds 6d, 6e, 6i, 6j, and 6m, did not exhibit significant cytotoxicity with IC₅₀ values above 85 µM for all compounds. Molecular docking studies of potent compounds 6d, 6e, 6i, 6j and 6m with DNA topoisomerase II revealed that they have a good affinity toward the target protein. In addition to this, in silico pharmacokinetic profile was achieved for the potent compounds 6d, 6e, 6i, 6j and 6m using SWISS/ADME and pkCSM, whereas 6d, 6e and 6i compounds followed Lipinski, Ghose, Veber, Egan, and Muegge rules without any deviation.

Keywords:

• Quinoxaline
• thiazole
• DNA topoisomerase-II
• anticancer activity
• ADMET

Acknowledgments

The authors are thankful to the Department of Chemistry, Chaitanya Deemed to be University for providing laboratory facilities and Department of Biotechnology, Chaitanya Deemed to be University for their support in anticancer activity.

Disclosure statement

No potential conflict of interest was reported by the author(s).