Interaction of Matrine alkaloid with human opioid receptors using docking molecular

FANNY ALVAREZ ESCALADA; LEDESMA A E

Congreso; L Reunión Anual SAB; 2022

Matrine (MT) alkaloid is a natural compound that present a wide range of pharmacologicalactivity [1]. It was previously reported the antinociceptive effect of matrine in mice [2]. These investigations suggest that MT exerts its antinociceptive effect mainly through the activation of Ƙ-opioid receptor (KOP) and partially through μ-opioid receptor (MOP) [3]. However, the antinociceptive effect of matrine in human has not yet been examined. The aim of this work is to investigate the affinity of matrine for Ƙ and μ human opioid receptors using docking molecular calculations. KOR and MOR human active form structures were obtained from the protein data bank and AutoDock 4.0 program was used to perform the docking and homology modeling of opioid receptors structures. Previously Matrine structure was optimized with DFT calculations using B3LYP basis set in Gaussian program package.Our results indicates that the amide group of matrine is the essential functional group todeterminate their biological activity. MT interacts with MOR (6DDF.pdb) through a hydrogen bond between the oxygen atom of amide group and the Met61 residue (distance of 2.11 Å) with a binding energy of -30,7 kJ/mol. Whereas in the binding site of Ƙ-opioid receptor (6b73.pdb) MT interacts with a binding energy of -34,6 kJ/mol and an inhibition constant (ki) of 0,79 μM. In the other hand, Asp138, Tyr320 and Met142 residues in KOP participated in the interaction with MT through hydrophobic interactions, similar results about the active site of this receptor were informed by Jin et al. [4]. Our results indicate that matrine interacts more strongly with Ƙ -opioid receptor. Althoughfurther experimental studies are needed to confirm these findings.