Exploring the anticancer potential of chromene-based thiosemicarbazones through in vitro, molecular docking, molecular dynamics simulation and DFT studies

Chromene derivatives have garnered significant attention in medicinal chemistry due to their diverse biological activities, including anticancer potential. In this study, two novel chromene-based thiosemicarbazone derivatives, ( E )-2-((4-chloro-2H-chromen-3-yl)methylene)- N -ethylhydrazine-1-carbothioamide ( 1 ) and ( E )- N -methyl-2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazine-1-carbothioamide ( 2 ), were synthesized and characterized using spectroscopic techniques. Crystal structures of both compounds were elucidated, revealing key hydrogen bonding patterns stabilizing the structures. Their biological activities were evaluated against a panel of cancer cell lines, with both compounds exhibiting selective cytotoxicity toward breast (MCF7 and MDA-MB-231) and bladder (T24) cancer cells while sparing normal cells (MCF-10a). Molecular docking and dynamics simulations demonstrated their ability to interact with the metabotropic glutamate receptor 5 (mGluR5), suggesting their potential as selective anticancer agents. Density Functional Theory (DFT) calculations provided insights into their electronic properties, reinforcing the observed structure-activity relationships. These findings highlight the therapeutic potential of chromene-based thiosemicarbazones and their promise as anticancer agents with high selectivity.