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Title |
Active compound from the leaves of vitex negundo L. shows anti-inflammatory activity with evidence of inhibition for secretory phospholipase A2 through molecular docking |
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Authors |
Thangaraj Vinuchakkaravarthy1*, Kaliya Perumal Kumaravel2, Samuthirapandian Ravichandran2,Devadasan Velmurugan11, 3* |
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Affiliation |
1Centre of Advanced Study in Crystallography & Biophysics, University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India; 2Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, Chidambaram-608 508, Tamil Nadu, India; 3Bioinformatics Infrastructure Facility (DBT-BIF), University of Madras, Guindy Campus, Chennai-600 025, Tamil Nadu, India;
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shirai2011@gmail.com; *Corresponding author
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Phone |
+91-9841075847; +91-44-22300122
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Fax |
+91-44-22352494
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Article Type |
Hypothesis
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Date |
Received September 13, 2011; Accepted September 20, 2011; Published October 14, 2011
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Abstract |
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 A2 (sPLA2s) 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 sPLA2 and Human non-pancreatic secretory PLA2 (Hnps PLA2) as targets to illustrate the anti-inflammatory and antidote activities of TDTBPP. Docking results showed hydrogen bond (H-bond) interaction with Lys69 residue lying in the anti-coagulant loop of D. russellis venom PLA2, 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 PLA2 structure showed coordination with calcium ion directly as well as through the catalytically important water molecule (HOH1260) located at the binding site.
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Keywords |
Vitex negundo, Tris(2,4-di-tert-butylphenyl) phosphate, Anti-inflammatory, Carrageenan, Antidote, PLA2, Induced Fit Docking
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Citation |
Vinuchakkaravarthy et al.
Bioinformation 7(4): 199-206 (2011) |
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Edited by |
P Kangueane
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ISSN |
0973-2063
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Publisher |
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License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License. |