RESUMO
In the course of our screening for antitrypanosomal compounds from soil microorganisms, as well as from the antibiotics library of the Kitasato Institute for Life Sciences, we found three peptide antibiotics, leucinostatin (A and B), alamethicin I and tsushimycin, which exhibited potent or moderate antitrypanosomal activity. We report here the in vitro and in vivo antitrypanosomal properties and cytotoxicities of leucinostatin A and B, alamethicin I and tsushimycin compared with suramin. We also discuss their possible mode of action. This is the first report of in vitro and in vivo trypanocidal activity of leucinostatin A and B, alamethicin I and tsushimycin.
Assuntos
Alameticina/farmacologia , Antibacterianos/farmacologia , Lipopeptídeos/farmacologia , Paecilomyces/metabolismo , Peptídeos/farmacologia , Tripanossomicidas , Tripanossomíase Africana/tratamento farmacológico , Alameticina/isolamento & purificação , Alameticina/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fermentação , Lipopeptídeos/isolamento & purificação , Lipopeptídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos ICR , Paecilomyces/classificação , Peptídeos/isolamento & purificação , Peptídeos/uso terapêutico , Peptídeos Cíclicos , Suramina/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Trypanosoma brucei rhodesiense/efeitos dos fármacos , Tripanossomíase Africana/parasitologiaRESUMO
No fluorescence of protoporphyrin IX (PpIX) was measured using a fiber optic probe in pigmented B16F10 melanoma in mice after topical application of 5-aminolevulinic acid methylester (ALA-Me). However, chemical extraction of tissues excised from mice after intratumoral administration of ALA-Me or its parent compound ALA revealed that this tumor had the capability to produce PpIX. Small amounts of endogenous porphyrins, mainly PpIX, were found in the melanoma not treated with these drugs. Topical application of ALA-Me followed by exposure with laser light (633nm) delayed the growth of the tumors slightly. Light alone also had a significant effect on the tumor growth.