Active compound from the leaves of Vitex negundo L. shows anti-inflammatory activity with evidence of inhibition for secretory Phospholipase A2 through molecular docking

摘要

Novel compounds with significant medicinal properties have gained much interest in therapeutic approaches for treating variousinflammatory disorders like arthritis, odema and snake bites and the post-envenom (impregnating with venom) consequences.Inflammation is caused by the increased concentration of secretory Phospholipases A2 (sPLA2s) at the site of envenom. A novelcompound Tris(2,4-di-tert-butylphenyl) phosphate (TDTBPP) was isolated from the leaves of Vitex negundo and the crystalstructure was reported recently. The acute anti-inflammatory activity of TDTBPP was assessed by Carrageenan-induced rat pawodema method. TDTBPP reduced the raw paw odema volume significantly at the tested doses of 50 mg/kg and 70 mg/kg bodyweight. Molecular docking studies were carried out with the X-ray crystal structures of Daboia russelli pulchella's (Vipera russelli,Indian Russell's viper) venom sPLA2 and Human non-pancreatic secretory PLA2 (Hnps PLA2) as targets to illustrate the antiinflammatoryand antidote activities of TDTBPP. Docking results showed hydrogen bond (H-bond) interaction with Lys69 residuelying in the anti-coagulant loop of D. russelli's venom PLA2, which is essential in the catalytic activity of the enzyme andhydrophobic interactions with the residues at the binding site (His48, Asp49). Docking of TDTBPP with Hnps PLA2 structureshowed coordination with calcium ion directly as well as through the catalytically important water molecule (HOH1260) located atthe binding site.