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, malate:quinone oxidoreductase ( MQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against MQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by sp. BioMCC f.T.8501 demonstrated stable 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 MQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited MQO activity at IC of 51 µM and 3D7 proliferation in vitro at IC of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian sp. BioMCC f.T.8501 as a novel inhibitor of MQO, which showed inhibitory activity against the proliferation of 3D7 in vitro.