Research Information System
3. ULUSLARARASI TIP VE ECZACILIK KONGRESİ, İstanbul, Turkey, 4 - 05 October 2025, pp.114, (Summary Text)
Natural compunds continue to be an important source of novel anticancer agents due to their structural complexity and bioactivity. In this study, a virtual screening of 4,787 small compounds annotated as “natural drug” in the ChEMBL database was performed against two critical apoptotic regulators: Bcl-2 and Caspase-3. Molecular docking was conducted using Maestro 14.3 (Schrödinger LLC, ÜSA). Threshold docking scores were defined as ≥ –8.0 kcal/mol for Bcl-2 and ≥ –6.0 kcal/mol for Caspase-3. A total of 37 molecules demonstrated dual activity by meeting both cutoffs. Among these, the top five candidates were further analyzed, revealing two common hits with particularly strong affinities: Talfirastide (Caspase-3 score –12.362, the highest; Bcl-2 score –8.362, 4th highest) and Bradykinin (Caspase-3 score –11.304, 5th highest; Bcl-2 score –9.545, the highest). Energetic and interaction profiling confirmed stable binding of both compounds within the active sites of the proteins. To further validate these findings, the molecular mechanics/generalized Born surface area (MM/GBSA) method was applied to estimate binding free energies, and the results revealed favorable ligand–protein affinities consistent with the docking scores. Taken together, these data strongly suggest that Talfirastide and Bradykinin may serve as dual modulators of apoptosis, simultaneously targeting pro- and anti-apoptotic pathways. The identification of natural compounds capable of engaging both Bcl-2 and Caspase-3 highlights their potential as scaffolds for apoptosis-inducing agents. Overall, this work underscores the promise of repurposing naturally derived molecules as dual-target regulators of cell death and provides a rational foundation for subsequent in vitro and in vivo studies aimed at developing novel anticancer therapeutics.