Antimalarial screening for microbial culture broth library

There is a strong global need for the development of malaria drugs.This stidy examined one strain of filamentous fungi selected by the above screening (a different strain from the previous year), and isolated five types of nitrogen-containing compounds as active substances. Three known compounds and two new compounds and their structures were determined by NMR and MS analysis. These five compounds inhibited the growth of multidrug-resistant malaria parasites by single-digit micromolars. In addition, two new cyclic peptide compounds discovered last year were reacquired by mass fermentation, and as a result of in vivo treatment experiments in malaria-infected mouse models, one compound reduced protozoan proliferation by approximately 50% at 30 mg/kg x 4, i.p. was found to interfere. In addition, no noticeable toxic symptoms were observed in mice, and it was expected to have a relatively high level of safety.

Screening was performed using the highly pathogenic Plasmodium falciparum multidrug-resistant strain K1 and normal human fibroblasts MRC-5. Samples with selective toxicity against protozoa were selected by evaluating the cytotoxicity against MRC-5 in the secondary screening of samples that showed antiprotozoan activity in the primary screening. Samples that passed the secondary screening were re-cultured and purified by various chromatography using antiprotozoan activity as an index. The chemical structure of the obtained active substance was clarified by instrumental analysis such as NMR and MS.

Project details

Basic Science
Product Development

Apr 2020 — Mar 2023

$36,954

Japan