Design and Synthesis of Novel Coumarin Conjugated Acetamides as Promising Anticancer Agents: An In Silico and In Vitro Approach

Background: Coumarin and benzophenone possess a vast sphere of biological activities, whereas thiazoles display various pharmacological properties. Hence, present study focused on the incorporation of coumarin and thiazole core to the benzophenone skeleton to enhance the bioactivity, anticipating their interesting biological properties. Objective: The objective of the current work is the synthesis and biological evaluation of a novel series of coumarin fused thiazole derivatives. Methods: A novel series of coumarin conjugated thiazolyl acetamide hybrid derivatives were synthesized by a multistep reaction sequence and were characterized by the FT-IR, LCMS, and NMR spectral techniques. The newly synthesized compounds were screened for anti-cancer activity by in-silico and in-vitro methods. The cytotoxicity of the synthesized unique compounds was executed for two different cancer cell lines, MCF-7 (Breast cancer) and KB (Oral cancer), in comparison with standard paclitaxel by MTT assay. Results: The compound 7f is a potent motif with an acceptable range of IC50 values, for anti-cancer activity, i.e., 63.54 mu g/ml and 55.67 mu g/ml, against the MCF-7 and KB cell lines, respectively. Molecule docking model revealed that this compound formed three conventional hydrogen bonds with the active sites of the amino acids, MET 769, ARG 817, and LYS 721. Conclusion: Compound 7f with two methyl groups on the phenoxy ring and one 4-position methoxy group on the benzoyl ring, showed a significant cytotoxic effect. An advantageous level of low toxicity against normal cell line (L292) by MTT assay was determined.

Automated summary

A novel series of coumarin fused thiazole derivatives were synthesized and evaluated for their anti-cancer activity in in vitro and in vivo experiments. Compound 7f showed low cytotoxicity and high anti-cancer activity, making it a promising candidate for further studies.