Novel chromone–hydrazone conjugates: Synthesis, in silico evaluation and cytotoxic assessment against hormone dependent breast cancer cell lines

Sant, Akrati and Kavya, K. M. and Parveen, Shama and Ahtsham, Ana and Krishnaveni, S. and Banerjee, Monisha and Bhatia, Sonika (2026) Novel chromone–hydrazone conjugates: Synthesis, in silico evaluation and cytotoxic assessment against hormone dependent breast cancer cell lines. Journal of Molecular Structure, 1353. p. 144636. ISSN 1872-8014

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Abstract

Given the structural resemblance of the benzopyran-4-one scaffold to 17β-estradiol, this study focused on the synthesis and evaluation of novel 3-formylchromone hydrazone derivatives as potential estrogen receptor-targeting anticancer agents. The compounds were synthesized via a two-step process using 3-formylchromone as a key intermediate and characterized by ¹H-NMR, ¹³C-NMR, FT-IR, and HRMS spectroscopy. Cytotoxicity was assessed against ER-positive MCF-7 and triple-negative MDA-MB-231 breast cancer cell lines, with HEK293 serving as a non-cancerous control. Within the series, compounds 3j, 3c, and 3e exhibited the highest potency against MCF-7 cells, with IC₅₀ values of 30 µM, 35 µM, and 37 µM, respectively. In contrast, these compounds showed markedly lower activity against MDA-MB-231 cells and displayed minimal cytotoxicity toward HEK293 cells. In silico pharmacokinetic profiling (SwissADME) confirmed favourable drug-like properties, including high gastrointestinal absorption, Lipinski’s rule compliance, and absence of PAINS alerts. Molecular docking indicated that compounds 3j and 3e aligned closely within the canonical 17β-estradiol binding pocket of estrogen receptor alpha (ERα), exhibiting significant overlap with the native ligand. These findings were further substantiated by molecular dynamics simulations, which confirmed the stability of the ligand–receptor interactions. DFT calculations revealed a low HOMO–LUMO energy gap for compound 3j (3.69 eV), indicating high reactivity and optimal electrostatic potential. Structure–activity relationship (SAR) analysis highlighted the role of electron-donating substituents in enhancing anticancer activity. Collectively, compounds 3j and 3e emerged as the most promising leads for further development as a targeted therapy for hormone-dependent breast cancer, with 3j being more potent.

Item Type:	Article
Uncontrolled Keywords:	3-formylchromones, Hydrazones, MCF-7, MDA-MB 231, Estrogen receptors,
Subjects:	D Physical Science > Physics
Divisions:	Department of > Physics
Depositing User:	C Swapna Library Assistant
Date Deposited:	20 Dec 2025 09:47
Last Modified:	20 Dec 2025 09:47
URI:	http://eprints.uni-mysore.ac.in/id/eprint/18234

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