RESUMO
More than 400 compounds isolated from soil microorganisms, and catalogued in the antibiotic library of the Kitasato Institute for Life Sciences, were screened against African trypanosomes. Ten compounds were found to have selective and potent antitrypanosomal activity in vitro: aureothin, cellocidin, destomycin A, echinomycin, hedamycin, irumamycin, LL-Z 1272beta, O-methylnanaomycin A, venturicidin A and virustomycin A. Results of the in vitro assays using the GUTat 3.1 strain of Trypanosomal brucei brucei and the STIB900 strain of T. b. rhodesiense are presented. Cytotoxicity was determined using a human MRC-5 cell line. This is the first report of antitrypanosomal activities of the 10 microbial metabolites listed above.
Assuntos
Tripanossomicidas/isolamento & purificação , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Alcinos/química , Alcinos/isolamento & purificação , Alcinos/metabolismo , Alcinos/farmacologia , Animais , Antraquinonas/química , Antraquinonas/isolamento & purificação , Antraquinonas/metabolismo , Antraquinonas/farmacologia , Linhagem Celular , Cromonas/química , Cromonas/isolamento & purificação , Cromonas/metabolismo , Cromonas/farmacologia , Equinomicina/química , Equinomicina/isolamento & purificação , Equinomicina/metabolismo , Equinomicina/farmacologia , Higromicina B/análogos & derivados , Higromicina B/química , Higromicina B/isolamento & purificação , Higromicina B/metabolismo , Higromicina B/farmacologia , Macrolídeos/química , Macrolídeos/isolamento & purificação , Macrolídeos/metabolismo , Macrolídeos/farmacologia , Naftoquinonas/química , Naftoquinonas/isolamento & purificação , Naftoquinonas/metabolismo , Naftoquinonas/farmacologia , Microbiologia do Solo , Tripanossomicidas/química , Tripanossomicidas/metabolismo , Venturicidinas/química , Venturicidinas/isolamento & purificação , Venturicidinas/metabolismo , Venturicidinas/farmacologiaRESUMO
Simaomicin alpha shows potent antimalarial activity in vitro and is known to be a cell-cycle effector. As erythrocytic schizogony of Plasmodium correlates with cell cycle events, we investigated the effect of simaomicin alpha on stage development of the malaria parasite Plasmodium falciparum. Simaomicin alpha interferes with normal parasite development in a time and concentration dependent manner. Parasites exposed to 2.5 nM simaomicin alpha at the ring stage or trophozoite stage showed disrupted development and immature schizont-like and segmenter-like forms were observed. However, schizont stage parasites were not affected by 2.5 nM simaomicin alpha. It is unclear whether mitosis involved in sequential parasite development occurred when parasites were exposed to simaomicin alpha at the ring or trophozoite stage. At a concentration of 5.0 nM, simaomicin alpha inhibited merozoite-trophozoite development. This concentration curtails p-LDH activity at all parasite stages, although its impact on the schizont stage is delayed for 24 hours.
Assuntos
Antimaláricos/farmacologia , Isoquinolinas/farmacologia , Plasmodium falciparum/efeitos dos fármacos , Animais , Ciclo Celular/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Plasmodium falciparum/citologia , Plasmodium falciparum/crescimento & desenvolvimentoRESUMO
Our on-going screening program to discover new antitrypanosomal antibiotics has been evaluating compounds isolated from soil microorganisms as well as investigating the antibiotic libraries of the Kitasato Institute for Life Sciences and BioFrontier Laboratories of Kyowa Hakko Kogyo Co., Ltd. We have now discovered two compounds, KS-505a and alazopeptin, which exhibit moderate antitrypanosomal characteristics. We report here the in vitro and in vivo antitrypanosomal activities and cytotoxicities of KS-505a and alazopeptin, compared with some commonly-used antitrypanosomal drugs. This is the first report of in vitro and in vivo antitrypanosomal activities of either KS-505a or alazopeptin.
