Selective activity of polyene macrolides produced by genetically modified Streptomyces on Trypanosoma cruzi.
The growth inhibitory effects on Trypanosoma cruzi of several natural tetraene macrolides and their derivatives were studied and compared with that of amphotericin B. All tetraenes strongly inhibited in vitro multiplication. Proliferation of epimastigotes was arrested by all these drugs at < or =3.6 microM, which were also active on amastigotes proliferating in fibroblasts. Compared with amphotericin B, the compounds were less effective but also less toxic, showing no effect on the proliferation of J774 and NCTC 929 mammalian cells at concentrations active against the parasites. CE-108B (a polyene amide) appeared to be an especially potent trypanocidal compound, with strong in vivo trypanocidal activity and very low or no toxic side effects, and thus should be considered for further studies.
Rolón
Miriam
M
Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Seco
Elena M
EM
Vega
Celeste
C
Nogal
Juan J
JJ
Escario
José A
JA
Gómez-Barrio
Alicia
A
Malpartida
Francisco
F
D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy; D005347:Fibroblasts / Q000187:drug effects; D018942:Macrolides / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D009005:Monosaccharides / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D010866:Natamycin / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D021261:Parasitic Sensitivity Tests; D011090:Polyenes / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism; D014344:Trypanocidal Agents / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
C485858:CE-108; D018942:Macrolides; D009005:Monosaccharides; D011090:Polyenes; D014344:Trypanocidal Agents; D000666:Amphotericin B; D010866:Natamycin