Antileishmanial activity of lapachol analogues.
The antileishmanial activity of lapachol, isolapachol, and dihydrolapachol, along with soluble derivatives (potassium salt) and acetate was obtained. All the compounds were assayed against metacyclic promastigotes of two different species of Leishmania associated to tegumentar leishmaniasis: L. amazonensis and L. braziliensis. All compounds presented significant activity, being isolapachol acetate the most active against promastigotes, with IC50/24h = 1.6 +/- 0.0 microg/ml and 3.4 +/- 0.5 microg/ml for, respectively, L. amazonensis and L. braziliensis. This compound was also assayed in vivo against L. amazonensis and showed to be active. Its toxicity in vitro was also established, and at concentration similar to the IC50, no toxicity was evidenced. In all experiments, pentamidine isethionate was used as a reference drug. The present results reinforce the potential use of substituted hydroxyquinones and derivatives as promising antileishmanial drugs and suggest a continuing study within this class of compounds.
Lima
Nadja M F
NM
Departamento de Química, CCEN, Universidade Federal de Alagoas, Tabuleiro do Martins, 57072-970 Maceió, AL, Brazil.
Correia
Clariane S
CS
Leon
Leonor L
LL
Machado
Gérzia M C
GM
Madeira
Maria de Fátima
Mde F
Santana
Antônio Euzébio G
AE
Goulart
Marília O F
MO
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D007892:Leishmania braziliensis / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000469:parasitology; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D013997:Time Factors
D000981:Antiprotozoal Agents; D009285:Naphthoquinones; C008252:lapachol