Effect of amidine derivatives on nitric oxide production by Leishmania amazonensis promastigotes and axenic amastigotes.
The effects of pentamidine isethionate (reference drug) and N,N'-diphenyl-4-methoxy-benzamidine (test compound) on NO. production by Leishmania amazonensis promastigotes and axenic amastigotes were investigated by measuring nitrite, a by-product of nitric oxide released into culture supernatants. The NO. production by infective promastigotes was inhibited by OCH(3)-amidine in about 23.53% and by pentamidine in only 3.78%. In axenic amastigotes, the inhibition of NO. production by OCH(3)-amidine was significantly higher (52.94%; p=0.01) than that by pentamidine, which inhibited this radical production nonsignificantly (25.29%; p=0.1). The mechanism of amidine derivatives, as an antimicrobial agent, is unknown. However, other amidines, such as a diamidine (pentamidine), contain chemical structures shared by the guanidino group of the nitric oxide synthase substrate L-arginine, suggesting the possibility of an interaction with this enzyme or electronic factors (substituent constant) that alter physical and chemical properties significant for biological activity.
Genestra
Marcelo
M
Department of Immunology, Oswaldo Cruz Institute, Fiocruz, Av. Brasil, 4365-CEP 926, Rio de Janeiro 21045-900, Brazil.
Echevarria
Aurea
A
Cysne-Finkelstein
Léa
L
Vignólio-Alves
Luciana
L
Leon
Leonor L
LL
D000578:Amidines / Q000378:metabolism* / Q000494:pharmacology*; D000818:Animals; D007894:Leishmania mexicana / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D007896:Leishmaniasis / Q000188:drug therapy / Q000469:parasitology; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D010419:Pentamidine / Q000494:pharmacology
D000578:Amidines; D009569:Nitric Oxide; D010419:Pentamidine