Multi-spectroscopic and molecular docking studies of human serum albumin interactions with sulfametoxydiazine and sulfamonomethoxine.

Abstract

Sulfonamides are a kind of antibiotics which have been widely used as feed additives for livestock and poultry. However, sulfa drugs have raised worldwide concerns because of their adverse impact on human health. In this study, two sulfonamides, sulfametoxydiazine (SMD) and sulfamonomethoxine (SMM), were selected to explore the binding modes with human serum albumin (HSA). The spectroscopic approaches revealed that SMD or SMM could spontaneously enter into the binding site I of HSA through hydrogen bond interactions and van der Waals forces, and that SMD exhibited much stronger binding affinity toward HSA than SMM at different temperatures (p<0.01, n=3). The binding constants for SMD-HSA and SMM-HSA were determined to be (8.297±0.010)×104L·mol-1 and (1.178±0.008)×104L·mol-1 at 298K, respectively. The interaction of SMD or SMM to HSA induced microenvironmental and conformational changes in HSA, where SMD had a greater effect on the α-helix content of HSA. Results from molecular docking implied that the amino acid residues of HSA, such as Arg222, Ala291 and Leu238, played key roles in the sulfonamide-HSA binding process. Meanwhile, hydrogen bonds might be a key factor contributing to the binding affinity of sulfa drugs and HSA. Additionally, the combined use of SMD and SMM led to an obvious variation in Ka values of binary systems (p<0.01, n=3). These findings might be helpful to understand the biological effects of sulfonamides in humans.