Selective and Potent in Vitro Antitrypanosomal Activities of Ten Microbial Metabolites

Abstract

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 1272b , Omethylnanaomycin 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.

Panowamycins A and B, new antitrypanosomal isochromans produced by Streptomyces sp. K07-0010

“…18 This strain, donated by Dr Y Yabu (Nagoya City University, Japan), is a clone derivative of a stock EVE (Edinburgh Veterinary Expedition) 10 that was originally isolated in 1966 from a naturally infected bovine in Uganda. Isolation of macrotetrolides from the culture broth of Streptomyces sp.…”

In vitro and in vivo antitrypanosomal activities of three peptide antibiotics: leucinostatin A and B, alamethicin I and tsushimycin

“…6,7 Animals Female CD1 mice (ICR), 20-25 g, were obtained from Charles River Japan Inc. (Kanagawa, Japan). Animals were placed in groups of four per cage, kept in a room under negative pressure with flow of 0.1-0.2 m sec À1 .…”

“…6,7 We have discovered a further three peptide antibiotics, leucinostatin A and B (produced by soil fungi, Paecilomyces sp.) and alamethicin I and tsushimycin (from the antibiotic library) (Figure 1), which show potent or moderate antitrypanosomal properties.…”

In vitro and in vivo antiprotozoal activities of bispolides and their derivatives

“…We have previously reported various microbial metabolites exhibiting potent antimalarial [1][2][3][4] and antitrypanosomal properties. [5][6][7] We have recently found that the known 20-membered ring macrodiolide antibiotics, the bispolides, 8 together with new derivatives, exhibit selective antitrypanosomal and potent antimalarial activities, both in vitro and in vivo. Here, we report the antitrypanosomal and antimalarial profiles of bispolides, their derivatives ( Figure 1) and the related 16-membered ring macrodiolide antibiotic as elaiophylin (azalomycin B) 9,10 (Figure 1) in comparison with those of clinically used antitrypanosomal drugs, such as suramin and eflornithine, and two clinically used antimalarial drugs, artemisinin and chloroquine.…”

“…The 13,13¢-dimethoxy compound, bispolide A3, prepared from bispolide A1 by reaction with 0.04%-HCl in MeOH, was reduced by NaBH 3 In vitro antiprotozoal activities against Trypanosoma brucei brucei strain GUTat 3.1, Plasmodium falciparum strains K1 (drugresistant) and FCR3 (drug-sensitive), and cytotoxicity against human diploid embryonic cell line MRC-5 were measured as described previously. 1, 5 In vivo antitrypanosomal activity for T. b. brucei strain S427 was measured as described previously. 6 Test compounds were solubilized in an aqueous mixture of 10% DMSO-Tween 80 and EtOH (7:3) and administered i.p.…”