SNAKE VENOM PHOSPHOLIPASES A2 INHIBITORS: MEDICINAL CHEMISTRY

ANDREIMAR MARTINS SOARES(1)

(1)Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, FCFRP, Universidade de São Paulo, USP, Ribeirão Preto-SP, Brazil.

Phospholipases A2 (PLA2s) are commonly found in snake venoms and have extensively studied due to their pharmacological and physiopathological effects in living organisms. The high medical-scientific concern evoked by the involvement of these proteins in different biological processes promoted an increasing search for natural or artificial inhibitors, aiding at PLA2s neutralization and a better understanding of their mode of action and their structure-function relationship. This article reports a minireview on natural and artificial inhibitors of enzymatic, toxic and pharmacological effects induced by snake venoms PLA2s. These inhibitors act on PLA2s through different mechanisms, most of them still not completely understood, including binding to specific domains, denaturation, modification of specific amino acid residues and others. Several substances have been evaluated to their effects against snake venoms and isolated toxins, including plant extracts and compounds from marine animals, mammals and snakes serum plasma, in addition to polyclonal antibodies and several synthetic molecules. Research involving these inhibitors may be useful to understand the mode of action of PLA2s and their role in envenomations caused by snake bite. Furthermore, the biotechnological potential of PLA2s inhibitors may provide therapeutic molecular models with antiophidian activity in supplementing to the conventional serum therapy against these multifunctional proteins.

KEY WORDS: phospholipases A2, phospholipases A2 inhibitors, natural and artificial inhibitors, snake venoms.

FINANCIAL SUPPORT: FAPESP and CNPq.

CORRESPONDENCE TO: Andreimar M. Soares, Depto. de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas – Ribeirão Preto, USP, Brazil. Phone: 55+ 16-36024714. E-mail: andreims@fcfrp.usp.br