1st International and 10th National Iranian Conference on Bioinformatics

Molecular docking and spectroscopic studies of sulfonamide-based imines with human serum albumin

Paper ID : 1415-ICB10

Authors:

Baran Mohamadi moghadam *¹, احمد امیری², آریا تجلی¹

¹دانشگاه تهران

²شیمی معدنی- دانشکده شیمی- دانشگاه تهران

Abstract:

Human serum albumin contains about 60% of the total plasma protein and commonly used to study drug-protein interactions. HSA shows high affinity to different drugs, nutrients, metal ions, and their metabolites. Based on materials’ affinity to HSA, their absorption, distribution, metabolism, and toxicity could be changed in vivo and then affect their pharmacokinetics, pharmacodynamics, and toxicity [1]. Sulfonamides are an important class of antibiotics, which have been widely used as feed additives in agriculture for decades [2].We report here, the synthesis of two sulfonamide ligands, SulfHB and SulfTP. The chemical structure of the ligands were dtetermined by different spectroscopic techniques. The binding modes of SulfHB and SulfTP ligands with HSA was explored experimentally and computationally. The fluorescence titration experiment revealed a strong complex formation between the ligands and HSA, with a significant quenching by a blue shift of ~18 nm at the λ max of 343.The molecular docking approaches revealed that SulfHB or SulfTP could spontaneously enter into the binding sites of HSA through H-bond interactions and van der Waals forces, and that SulfHB exhibited much stronger binding affinity toward HSA than SulfTP at different temperatures (ΔG =-11.29 for SulfHB, and ΔG = -9.52 for SulfTP). The binding constants for SulfTP-HSA were determined to be 39.95 × 10 5 L.mol −1 at 298 K., and SulfHB had a greater effect on the α-helix content of HSA. Observations from molecular docking studies revealed that the hydrogen bonds might be a key factor contributing to the binding affinity of sulfa drugs and HSA. The aminoacids such as Arg117, Asn130, Asp129, Lys199, Ala 297 and Arg222, play key roles in the sulfonamide-HSA binding process via their interaction with the sulfone (O=S=O) and hydroxyl groups of the ligands. These findings might be helpful to understand the biological effects of sulfonamides in humans.

Keywords:

HSA; Sulfa Drugs; Molecular Docking; DFT-BPV86; GAUSSIAN; Sulfadiazine

Status : Paper Accepted (Poster Presentation)