Novel apigenin based small molecule that targets snake venom metalloproteases

Srinivasan, V. and Sundaram, M. S. and Sebastian Anusha, and Hemshekhar, M. and Nayaka, S. Chandra and Kemparaju, K. and Basappa, and Girish, K. S. and Rangappa, K. S. (2014) Novel apigenin based small molecule that targets snake venom metalloproteases. PloS One, 9 (9). pp. 1-11. ISSN 1932-6203

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Official URL: http://dx.doi.org/10.1371/journal.pone.0106364

Abstract

The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available.Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including an aphylaxis,serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to off setviper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues aresynthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC)venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological studyfurther conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and both ropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound5d could be a potent agent in viper bite management.

Item Type: Article
Subjects: Agriculture Biological Sciences > Biochemistry
University of Mysore > PG Campuses > Manasagangotri, Mysore > Agriculture Biological Sciences > Biochemistry

Agriculture Biological Sciences > Biotechnology
University of Mysore > PG Campuses > Manasagangotri, Mysore > Agriculture Biological Sciences > Biotechnology

Physical Sciences > Chemistry
Divisions: PG Campuses > Manasagangotri, Mysore > Biochemistry
PG Campuses > Manasagangotri, Mysore > Biotechnology
PG Campuses > Manasagangotri, Mysore > Chemistry
Depositing User: Praveen Kumari B.L
Date Deposited: 02 Mar 2015 07:13
Last Modified: 02 Mar 2015 07:13
URI: http://eprints.uni-mysore.ac.in/id/eprint/17549

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