Synthesis and Biological Evaluations of N-(4-Substituted Phenyl)-7-Hydroxy-4-Methyl-2-Oxoquinoline-1(2H)-Carbothioamides

Abstract

In continuance of search for new compounds we report herein the expedient and optimized synthesis of a series of N-(4-substituted phenyl)-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-carbothioamides (5a-g) in good yields. The anticancer and antioxidant activities were determined as per the standard protocol. Nearly 5 dozens of cancer cell lines derived from nine different panels are used in the study and anticancer activity was calculated as growth percents (GPs) and percent growth inhibitions (%GIs). The molecular docking simulation against one of the potential targets i.e., epidermal growth factor receptor (EGFR) was done to find the putative approach of action of the title compounds 5a-g. N-(4-Nitrophenyl)-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)-carbothioamides (5b) showed the most promising anticancer activity with higher sensitivity against UO-31, HOP-92, CAKI-1, LOX IMVI and T-47D with GPs of 66.65, 72.63, 85.80, 86.11, and 86.96 respectively. The compound 5b exhibited antioxidant activity with an IC₅₀ value of 15.21 ± 1.52 µM. The molecular docking simulation showed an efficient binding of compound 5b against the activity site of EGFR with two H-bond interactions with the residues Gln791 and Thr854, a π-π stacking and a π-cationic interaction with the residue Phe856, while a salt bridge interaction with the residue Lys745.

Graphical Abstract

Keywords:

• Anticancer
• antioxidant
• EGFR
• oxoquinoline

Acknowledgements

The author Dr Abuzer Ali is thankful to Taif University Researchers Supporting Project Number (TURSP-2020/124), Taif University, Taif, Saudi Arabia. The authors also acknowledge the help of National Cancer Institute USA in anticancer activity. The authors are grateful to Schrodinger for providing a trial license, and training team.

Disclosure statement

The authors declared no conflict of interest.

Additional information

Funding

The author Dr Abuzer Ali is thankful to Taif University Researchers Supporting Project Number (TURSP-2020/124), Taif University, Taif, Saudi Arabia. The authors also acknowledge the help of National Cancer Institute USA in anticancer activity. The authors are grateful to Schrodinger for providing a trial license, and training team