DFT and molecular docking investigations of metformin interactions with spermine oxidase

Abstract

This study used DFT and molecular docking calculations, in combination with in vitro examinations, to explore the interaction between Metformin (MET) and Human Spermine Oxidase (SMOX). The crystal structure of SMOX (7OXL) was obtained from the Protein Data Bank. Five bioactive compounds derived from Metformin were used to analyze the binding interactions with 7OXL protein and to explore additional information on the structure-activity relationship. DFT calculations were used to obtain the optimized structures of the target compounds at the B3LYP/ 6-311G(d, p) level of theory. Molecular docking calculations show that MET exhibits a significant binding score of -5.8 kcal.mol^− 1 by forming three hydrogen bonds in the active site of SMOX. Experimentally, UV spectrophotometric results confirmed these computational estimates and showed that MET can successfully inhibit SMOX activity with an IC50 of 16 × 10^− 4 M. Furthermore, the kinetic analysis demonstrated a competitive inhibition mechanism, supported by an increase in Km from 126.58 to 263.15 mM, while Vmax remained constant at 0.108 U/ml. The use of both theoretical and experimental evaluations showed that MET is a competitive inhibitor of SMOX, providing valuable information on the structure-activity relationship for future drug design.