Nornidulin, A New Inhibitor of Plasmodium falciparum Malate: Quinone Oxidoreductase ( Pf MQO) from Indonesian Aspergillus sp. BioMCC f.T.8501.

This study aimed to obtain a microbial active compound as a novel antimalarial drug from Indonesian isolates. Target-based assays were used to screen for antimalarial activity against the parasite mitochondrial, Plasmodium falciparum malate:quinone oxidoreductase ( Pf MQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against Pf MQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by Aspergillus sp. BioMCC f.T.8501 demonstrated stable Pf MQO inhibitory activity. Several purification stages, including OCC, TLC, and HPLC, were performed to obtain bioactive compounds from this active extract. All purification steps were followed by an assay against Pf MQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited Pf MQO activity at IC 50 of 51 µM and P. falciparum 3D7 proliferation in vitro at IC 50 of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian Aspergillus sp. BioMCC f.T.8501 as a novel inhibitor of Pf MQO, which showed inhibitory activity against the proliferation of P. falciparum 3D7 in vitro.