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.
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.
Antimalarial activities have been identified in four microbial metabolites through a screening programme of existing compounds in the Kitasato Institute chemical library. Hedamycin showed selective and potent activity against both drug-resistant and drug-sensitive strains of Plasmodium falciparum. Simaomicin a exhibited remarkably strong antimalarial activity, although its activity against a drug-resistant strain was weaker than that against a drugsensitive strain. The antimalarial effects of triacsins C and D are also reported. Keywords antimalarialantibiotics, hedamycin, simaomicin a , triacsin, Plasmodium falciparum, drugresistant strain As a result of our on-going program of screening soil microorganisms and renewed testing of compounds lodged in the antibiotic library of the Kitasato Institute for Life Sciences, we have previously reported on various microbial metabolites that exhibit potent antimalarial activities [1ϳ5]. We have now discovered four more compounds that possess antimalarial characteristics. Hedamycin, simaomicin a , triacsin C and triacsin D, all from the antibiotic library of the Kitasato Institute, display potent antimalarial activity in vitro. We report here the antimalarial profiles of these four compounds (Fig. 1) [6ϳ8] in comparison with those of clinically-used antimalarial drugs.In vitro activities against Plasmodium falciparum strains K1 (drug-resistant) and FCR3 (drug-sensitive), and cytotoxicity against human diploid embryonic cell line MRC-5 of these compounds, were measured as described previously [1].Hedamycin showed weak activity against both the K1 and FCR3 strain of P. falciparum, similar to the activity of chloroquine for K1 strain (Table 1). The IC 50 value of chloroquine to the K1 strain is 10-fold higher than to the FCR3 strain, indicating that the antimalarial action of hedamycin is different from that of chloroquine. Although the compound does not meet the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) criteria for whole cell screening (IC 50 Ͻ0.1 mg/ml for P. falcipurum K1 strain), it could be a promising lead if the activity could be improved since it has low cytotoxicity (IC 50 Ͼ25 mg/ml).Simaomicin a showed the most potent activity against both drug-resistant K1 and drug-sensitive FCR3. The IC 50 values of the compound were remarkably lower than those of the clinically-used antimalarial drugs, artemether, artemisinin and chloroquine. The cytotoxicity of the compound was weaker (IC 50 ϭ4 ng/ml) than its antimalarial activities. Simaomicin a was 4.6-fold less active against the K1 strain than the FCR3 strain. Although simaomicin a showed considerably more potent antimalarial activity than that of the other compounds, the presence of a polycyclic xanthone structure containing an isoquinoline moiety may
Recent research on human behavior has often collected empirical data from the online labor market, through a process known as crowdsourcing. As well as the United States and the major European countries, there are several crowdsourcing services in Japan. For research purpose, Amazon's Mechanical Turk (MTurk) is the widely used platform among those services. Previous validation studies have shown many commonalities between MTurk workers and participants from traditional samples based on not only personality but also performance on reasoning tasks. The present study aims to extend these findings to non-MTurk (i.e., Japanese) crowdsourcing samples in which workers have different ethnic backgrounds from those of MTurk. We conducted three surveys (N = 426, 453, 167, respectively) designed to compare Japanese crowdsourcing workers and university students in terms of their demographics, personality traits, reasoning skills, and attention to instructions. The results generally align with previous studies and suggest that non-MTurk participants are also eligible for behavioral research. Furthermore, small screen devices are found to impair participants' attention to instructions. Several recommendations concerning this sample are presented.
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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.