Snake venom phospholipase A2 inhibitors: medicinal chemistry and therapeutic potential.
Phospholipases A2 (PLA2s) are commonly found in snake venoms from Viperidae, Hydrophidae and Elaphidae families and have been extensively studied due to their pharmacological and physiopathological effects in living organisms. This article reports a review on natural and artificial inhibitors of enzymatic, toxic and pharmacological effects induced by snake venom 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 regarding their effects against snake venoms and isolated toxins, including plant extracts and compounds from marine animals, mammals and snakes serum plasma, in addition to poly or monoclonal antibodies and several synthetic molecules. Research involving these inhibitors may be useful to understand the mechanism of action of PLA2s and their role in envenomations caused by snake bite. Furthermore, the biotechnological potential of PLA2 inhibitors may provide therapeutic molecular models with antiophidian activity to supplement the conventional serum therapy against these multifunctional enzymes.
Marcussi
Silvana
S
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto-SP, Brazil.
Sant'Ana
Carolina D
CD
Oliveira
Clayton Z
CZ
Rueda
Aristides Quintero
AQ
Menaldo
Danilo L
DL
Beleboni
Rene O
RO
Stabeli
Rodrigo G
RG
Giglio
José R
JR
Fontes
Marcos R M
MR
Soares
Andreimar M
AM
D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D012910:Snake Venoms / Q000201:enzymology*
D004791:Enzyme Inhibitors; D012910:Snake Venoms; D010741:Phospholipases A; D054467:Phospholipases A2