In silico Design, Synthesis and Biological Evaluation of Novel Chalcone Derivatives as Potent Tubulin-Targeting Anticancer Agents

Asian Journal of Chemistry, Journal Year: 2025, Volume and Issue: 37(4), P. 882 - 892

Published: March 29, 2025

Tubulin is an essential protein involved in microtubule dynamics that regulate mitotic cell division normal cells. Specifically, the colchicine-binding site of tubulin serves as a therapeutic target to disrupt dynamics, inducing arrest and leading death. In current study, we synthesized methoxy fluorine substituted novel chalcones (4a-o) chalcone compounds showed promising anticancer activity by vitro viability using MTT assay lung cancer (A549) breast (MCF-7) lines silico docking simulations along with optimization drug-like pharmacokinetic properties. Among all compounds, (E)-1-(4,6-dimethoxybenzofuran-2-yl)-3-(4-methoxyphenyl)prop-2-en-1-one (4f) had highest potency (IC50 = 23.9 ± 0.203 µM), followed compound (E)-1-(4,6-dimethoxybenzofuran-2-yl)-3-(2,4,6-trifluorophenyl)prop-2-en-1-one (4m) value 35.44 µM). Moreover, 4f demonstrated excellent interaction (-9.94 kcal/mol) key residues Met-259, Leu-255 Ala-250 at pocket against millepachine, which similar millepachine binding tubulin, suggesting mechanism action may potentially affect dynamics. Additionally, identified properties, physico-chemical characteristics.

Language: Английский

Novel benzofuran-conjugated indolin-2-ones as anticancer agents; design, synthesis, biological assessments, and molecular modeling insights

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108494 - 108494

Published: April 1, 2025

Language: Английский