Anti-Serine/threonine-protein kinase-۴ Potential of some Cannabis Extract compounds: In Silico Study

The increasing prevalence of diabetes is one of the most important health challenges worldwide. Serine/threonine-protein kinase-۴ (STK۴) is important in various cellular processes, with particularly in diabetes. Cannabis is a plant species that contains various medicinal compounds. This study aimed to examine whether the six compounds found in Cannabis extract can inhibit the STK۴ protein that is present in diabetes. The crystallized structure (.pdb format) of Cannabis extract compounds were obtained from the PubChem database and used as ligands. Using the mm۲ method, the ligand's structure was optimized. AutodockVina was employed to assess the ligand's effectiveness as an inhibitor against the active site of STK۴ chain A and B. The results generated were analyzed and evaluated using Discovery Studio v۱۶.۱.۰ software. Toxicity prediction of the best inhibitor was done by ProTox-II. The best affinity was obtained against ۶YAT -chain A by -۹.۱ kcal/mol. The highest diversity of links was also reported in Ligand C with ۶YAT -chain A. Hydrogen bonds established with ۶YAT -chain A against Tyrosine: ۱۰۴, Arginine: ۲۴۵ and Phenylalanine: ۲۴۴, indicating the effectiveness of delta(۹)-Tetrahydrocannabinolic acid against chain A of ۶YAT. Toxicity prediction showed that all pharmacokinetic parameters of ligand C molecule are in the acceptable range. Our study can provide valuable information about newly identified inhibitors for the treatment of diabetes. The findings of this study indicated that delta (۹)-Tetrahydrocannabinolic acid molecule could be used as a novel STK۴ inhibitor in the future studies.