Novel compounds with significant medicinal properties have gained much interest in therapeutic approaches for treating various inflammatory 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 A(2) (
sPLA(2)s) at the site of envenom. A novel compound Tris(2,4-di-tert-butylphenyl)
phosphate (TDTBPP) was isolated from the leaves of Vitex negundo and the crystal structure was reported recently. The acute anti-inflammatory activity of TDTBPP was assessed by
Carrageenan-induced rat paw odema method. TDTBPP reduced the raw paw odema volume significantly at the tested doses of 50 mg/kg and 70 mg/kg
body weight. Molecular docking studies were carried out with the X-ray crystal structures of Daboia russelli pulchella's (Vipera russelli, Indian
Russell's viper) venom sPLA(2) and Human non-pancreatic secretory PLA(2) (Hnps PLA(2)) as targets to illustrate the antiinflammatory and
antidote activities of TDTBPP. Docking results showed hydrogen bond (H-bond) interaction with Lys69 residue lying in the anti-
coagulant loop of D. russelli's
venom PLA(2), which is essential in the catalytic activity of the
enzyme and hydrophobic interactions with the residues at the binding site (His48, Asp49). Docking of TDTBPP with Hnps PLA(2) structure showed coordination with
calcium ion directly as well as through the catalytically important water molecule (HOH1260) located at the binding site.