Sulfur Compounds as Inhibitors of Enzymatic Activity of a Snake Venom Phospholipase A<sub>2</sub>: Benzyl 4-nitrobenzenecarbodithioate as a Case of Study
Snakebite is a neglected disease with a high impact in tropical and subtropical countries. Therapy based on antivenom has limited efficacy in local tissue damage caused by venoms. Phospholipases A<sub>2</sub> (PLA<sub>2</sub>) are enzymes that abundantly occur in snake venoms...
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| Autores principales: | , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2020
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/107866 http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC7144397&blobtype=pdf https://www.mdpi.com/1420-3049/25/6/1373 |
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| Sumario: | Snakebite is a neglected disease with a high impact in tropical and subtropical countries. Therapy based on antivenom has limited efficacy in local tissue damage caused by venoms. Phospholipases A<sub>2</sub> (PLA<sub>2</sub>) are enzymes that abundantly occur in snake venoms and induce several systemic and local effects. Furthermore, sulfur compounds such as thioesters have an inhibitory capacity against a snake venom PLA<sub>2</sub>. Hence, the objective of this work was to obtain a carbodithioate from a thioester with known activity against PLA<sub>2</sub> and test its ability to inhibit the same enzyme. Benzyl 4-nitrobenzenecarbodithioate (I) was synthesized, purified, and characterized using as precursor 4-nitrothiobenzoic acid S-benzyl ester (II). Compound I showed inhibition of the enzymatic activity a PLA<sub>2</sub> isolated from the venom of the Colombian rattlesnake <i>Crotalus durissus cumanensis</i> with an IC<sub>50</sub> of 55.58 µM. This result is comparable with the reported inhibition obtained for II. Computational calculations were performed to support the study, and molecular docking results suggested that compounds I and II interact with the active site residues of the enzyme, impeding the normal catalysis cycle and attachment of the substrate to the active site of the PLA<sub>2</sub>. |
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