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Vol. 37 No. 4 (2025): Vol 37 Issue 4, 2025

Copyright (c) 2025 Somdutt Mujwar, kailash Rani, Vipin Kumar, Rakesh Kumar Sindhu

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This work is licensed under a Creative Commons Attribution 4.0 International License.

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

https://doi.org/10.14233/ajchem.2025.33499
Kailash Rani
Department of Pharmaceutical Chemistry, Chitkara College of Pharmacy, Chitkara University, Rajpura-140401, India
https://orcid.org/0009-0009-9652-3087
Vipin Kumar
Broad Institute of MIT and Harvard. Cambridge, MA 02142, USA
https://orcid.org/0000-0003-2533-9089
Rakesh Kumar Sindhu
Department of Pharmacognosy and Phytochemistry, Sharda School of Pharmacy, Sharda University, Greater Noida-201310, India
https://orcid.org/0000-0003-2619-4643
Somdutt Mujwar
Department of Pharmaceutical Chemistry, Chitkara College of Pharmacy, Chitkara University, Rajpura-140401, India
https://orcid.org/0000-0003-4037-5475

Corresponding Author(s) : Somdutt Mujwar

somduttmujwar@gmail.com

Asian Journal of Chemistry, Vol. 37 No. 4 (2025): Vol 37 Issue 4, 2025

Abstract

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

Keywords

Chalcone Tubulin Anticancer activity Molecular docking ADMET
(1)
Rani, K.; Kumar, V.; Sindhu, R. K.; Mujwar, S. In Silico Design, Synthesis and Biological Evaluation of Novel Chalcone Derivatives As Potent Tubulin-Targeting Anticancer Agents. ajc 2025, 37, 882-892.
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