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

Emirdağ S., Ulusoy N. G., KAHRİMAN N., SERDAROĞLU V., TÜRKMENOĞLU B., YAYLI N.

Journal of Molecular Structure, vol.1345, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1345
  • Publication Date: 2025
  • Doi Number: 10.1016/j.molstruc.2025.143101
  • Journal Name: Journal of Molecular Structure
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Keywords: ADME docking, Chalcone, Gypsogenin, Natural product, Semisynthesis
  • Karadeniz Technical University Affiliated: Yes

Abstract

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 μM (A19, A549), 1.04 ± 0.02 μM (A25, HeLa), 0.90 ± 0.14 μM (A25, HEK293), 0.25 ± 0.03 μM (A25, SHSY5Y), 1.18 ± 0.03 μM (A26, MDA-MB-231), and 0.99 ± 0.03 μM (A26, PANC-1). Likewise, hybrid derivatives C12, C14, and C26 exhibited higher antiproliferative activity than doxorubicin, with IC50 values of 1.33 ± 1.14 μM (C26, A549), 9.51 ± 0.03 μM (C12, HeLa), 4.09 ± 0.65 μM (C26, HEK293), 1.79 ± 0.09 μM (C12, SHSY5Y), 7.97 ± 0.84 μM (C26, MDA-MB-231), and 3.71 ± 0.49 μM (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.