Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1364, 2026 (SCI-Expanded, Scopus)
AbstractLactate dehydrogenase A (LDH-A) plays a crucial role in glycolysis by catalyzing the interconversion of lactate and pyruvate. Since cancer cells preferentially utilize glycolysis over oxidative phosphorylation—a phenomenon known as the Warburg effect—LDH-A has become a key target in cancer therapy. In this study, novel derivatives containing a norcantharimide scaffold were synthesized and structurally confirmed by FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. Their inhibitory effects against LDH-A were evaluated in vitro, revealing compound 6b as the most potent inhibitor (IC₅₀ = 138.6 µM). Molecular docking studies demonstrated strong binding affinities to the NADH binding site of LDH-A, primarily via hydrogen bonding and hydrophobic interactions, supported by favorable Moldock scores. Molecular dynamics simulations further confirmed the stability of the ligand-enzyme complexes for 6b Furthermore, ABTS radical scavenging and metal chelation assays were performed to further characterize the biological activity profile of the synthesized compounds. ADME predictions suggested acceptable pharmacokinetic profiles. These results establish 6b as the lead candidate, highlighting that targeted functional flexibility outweighs static stability metrics in LDH-A inhibition.