Title:Design and Synthesis of Novel Coumarin Conjugated Acetamides as Promising Anticancer Agents: An In Silico and In Vitro Approach
Volume: 21
Issue: 11
Author(s): S.V. Mamatha*, Shiddappa L. Belagali, Mahesh Bhat and Vijay M. Kumbar
Affiliation:
- Department of Studies in Environmental Science, Environmental Chemistry Section, University of Mysore, Manasagangothri, Mysuru- 570 006, Karnataka,India
Keywords:
Coumarin, acetamides, thiazole, anti-cancer, benzophenone, in silico.
Abstract:
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.,
63.54μg/ml and 55.67μg/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.
