ADME predictions and molecular docking insights for novel Gypsogenin-chalcone hybrids and chalcones as antitumor and antimicrobial agents

The cytotoxicity and antimicrobial efficacy of novel semisynthesized Gypso-Anhd chalcone hybrids (C1-C27) and methoxy-substituted hydroxychalcones (A1-A27) were evaluated in the following six cancer cell lines: A549, HeLa, HEK293, SHSY5Y, MDA-MB-231, and PANC-1. These derivatives exhibited significant antimicrobial activity, against G+ bacteria (Bacillus subtilis, Enterococcus faecalis, and Staphylococcus aureus), G-bacteria (Escherichia coli and Pseudomonas aeruginosa) and Candida albicans. Among hydroxychalcone derivatives, A19, A25, and A26, demonstrated superior antiproliferative activity compared doxorubicin, with IC50 values of 1.43 + 0.02 mu M (A19, A549), 1.04 + 0.02 mu M (A25, HeLa), 0.90 + 0.14 mu M (A25, HEK293), 0.25 + 0.03 mu M (A25, SHSY5Y), 1.18 + 0.03 mu M (A26, MDA-MB-231), and 0.99 + 0.03 mu M (A26, PANC-1). Likewise, hybrid derivatives C12, C14, and C26 exhibited higher antiproliferative activity than doxorubicin, with IC50 values of 1.33 + 1.14 mu M (C26, A549), 9.51 + 0.03 mu M (C12, HeLa), 4.09 + 0.65 mu M (C26, HEK293), 1.79 + 0.09 mu M (C12, SHSY5Y), 7.97 + 0.84 mu M (C26, MDA-MB-231), and 3.71 + 0.49 mu M (C14, PANC-1). Molecular docking studies confirmed target-specific interactions for all synthesized derivatives. ADME analyses indicated favorable pharmacokinetic profiles, while hydroxy and methoxy substitutions modulated bioactivity, highlighting their potential as anticancer drug candidates.