Non-toxic fractions of streptomyces hygroscopicus subsp. hygroscopicus metabolite suppressed the growth of plasmodium falciparum in vitro possibly through l-malate: Quinone oxidoreductase (pfmqo) mitochondrial enzyme inhibition

Introduction: Previous research has proven that ethyl acetate extract of Streptomyces hygroscopicus can inhibit Plasmodium growth in vivo and in vitro through inhibition of the Proteasome ubiquitin system. In this study, we analyzed the activity of several fractions of S. hygroscopicus toward the growth of P. falciparum culture with specific targets on the mitochondrial enzyme of P. falciparum; L-malate: Quinone oxidoreductase (PfMQO) and dihydroorotate dehydrogenase (PfDHODH). Methodology: The fractionation process uses the Flash Column Chromography (FCC) BUCHI Reveleris® PREP, analyzed using thin layer chromatography (TLC). The antimalarial activity of the fractions was tested on the culture of P. falciparum 3D7 using enzyme lactate dehydrogenase (PfLDH) assay and their activity toward PfMQO and PfDHODH target enzymes. The fractions analyzed using HPLC and compared to the standard dihydroeponemycin. The toxicity of the fractions, the WST-8 assay was conducted. Results: Of the 30 fractions produced, 6 fractions were able to suppress the P. falciparum and two of them were able to inhibit more than 50% of P. falciparum growth. Both of these fractions were proven to inhibit the activity of the PfMQO enzyme but had no inhibition of the PfDHODH enzyme. Both fractions reduced human cell viability by less than 50% in toxicity test. HPLC analysis indicated that besides dehydroeponemycin, there were other compounds presences in the extract. Conclusions: Fractions of S. hygroscopicus metabolite contains non-toxic compounds in addition to dihydroeponemycin that could suppress the growth of P. falciparum in vitro. This potential effect might be related to the inhibition of PfMQO enzyme.