2nd Edition of Pharma R&D and Drug Discovery World Conference 2026

Abstract

Drugs are mainly transported to target tissues by plasma proteins, such as human serum albumin (HSA) and transferrin. HSA, the most abundant protein in plasma, is a critical carrier for drugs, dyes, and ions, making drug–HSA interaction analysis a priority in pharmacology. In addition, many anticancer drugs exert biological activity through DNA binding. This study investigated the interaction of Fusaro chromanone (FC101g), a potent anticancer mycotoxin, with two key biomacromolecules—DNA and HSA—using a combination of experimental spectroscopic methods and molecular docking. UV-Vis spectroscopy showed a hypochromic effect for DNA with a slight wavelength shift, indicating groove binding, and a drop in HSA absorption suggested changes in HSA’s structure upon drug binding. Fluorescence spectroscopy revealed static quenching for both DNA and HSA. The interaction with DNA mainly involved van der Waals and hydrogen bonds, while the binding to HSA was mostly due to hydrophobic bonds. Thermodynamic analysis confirmed that binding occurs spontaneously, with different contributions of enthalpy and entropy for each biomolecule. Competitive fluorescence tests with Hoechst 33258 confirmed that FC101g prefers the DNA minor groove. Competition assays with warfarin and ibuprofen identified the IA/IB subdomain (Sudlow’s site I) as the HSA binding site. CD spectroscopy showed minor structural changes in DNA, further supporting groove binding, and there were conformational changes in HSA that suggested an increase in α-helical content. Viscosity measurements showed little change in DNA length, again supporting groove binding. Molecular docking backed up these results, placing FC101g in the DNA minor groove and in the hydrophobic regions of HSA. Overall, the combined spectroscopic and computational methods demonstrated that FC101g binds to DNA through the minor groove via van der Waals and hydrogen bonds, and to HSA through hydrophobic interactions at Sudlow’s site I. These findings enhance our understanding of how FC101g binds, which could inform strategies for drug delivery and the design of anticancer drugs