title: Vanillin analog--vanillyl mandelic acid, a novel specific inhibitor of snake venom 5'-nucleotidase.
abstract: Snake venom 5'-nucleotidase (5'NUC) plays a very important role in envenomation strategies; however, apart from its modulation of hemostatic functions, its other pharmacological effects are not yet well characterized. Several studies have used specific inhibitors of enzyme toxins as a biochemical or pharmacological tool to characterize or establish its mechanism of action. We report here for the first time vanillin mandelic acid (VMA), an analog of vanillin, to potentially, selectively, and specifically inhibit venom 5'NUC activity among other enzymes present in venoms. VMA is much more potent in inhibiting 5'NUC activity than vanillyl acid (VA). The experimental results obtained are in good agreement with the in silico molecular docking interaction data. Both VA and VMA are competitive inhibitors as evident by the inhibition-relieving effect upon increasing the substrate concentration. VMA also dose-dependently inhibited the anticoagulant effect in Naja naja venom. In this study, we report novel non-nucleoside specific inhibitors of snake venom 5'NUC and experimentally demonstrate their involvement in the anticoagulant activity of N. naja venom. Hence, we hypothesize that VMA can be used as a molecular tool to evaluate the role of 5'NUC in snake envenomation and to develop prototypes and lead compounds with potential therapeutic applications against snake bites.
authors.affiliation: Department of Bioinformatics, SCBT, SASTRA University, Thirumalaisamudram, Thanjavur, India.
authors.forename: Raghaven
authors.initials: R
authors.lastname: Arun
authors.forename: Abdul Salam Syed Yasir
authors.initials: AS
authors.lastname: Arafat
authors.forename: Cletus J M
authors.initials: CJ
authors.lastname: D'Souza
authors.forename: Venkatabalasubramanian
authors.initials: V
authors.lastname: Sivaramakrishnan
authors.forename: Bhadrapura Lakkappa
authors.initials: BL
authors.lastname: Dhananjaya
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors*; D001547:Benzaldehydes / Q000737:chemistry*; D001667:Binding, Competitive; D001777:Blood Coagulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005340:Fibrinogen / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011485:Protein Binding; D012909:Snake Bites / Q000188:drug therapy; D012910:Snake Venoms / Q000201:enzymology*; D014642:Vanilmandelic Acid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001547:Benzaldehydes; D004791:Enzyme Inhibitors; D012910:Snake Venoms; D014642:Vanilmandelic Acid; D005340:Fibrinogen; C100058:vanillin; D015720:5'-Nucleotidase
keywords: 5′-Nucleotidase; Anticoagulant; Purines; Snake venoms; Vanillyl mandelic acid