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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, <i>Plasmodium falciparum</i> malate:quinone oxidoreductase (<i>Pf</i>MQO) enzyme. In total, 1600 crude extracts, composed from 800 fungi and 800 actinomycetes extracts, were screened against <i>Pf</i>MQO, yielding six active extracts as primary hits. After several stages of stability tests, one extract produced by <i>Aspergillus</i> sp. BioMCC f.T.8501 demonstrated stable <i>Pf</i>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 <i>Pf</i>MQO. We identified the active compound as nornidulin based on its LC-MS and UV spectrum data. Nornidulin inhibited <i>Pf</i>MQO activity at IC₅₀ of 51 µM and <i>P. falciparum</i> 3D7 proliferation in vitro at IC₅₀ of 44.6 µM, however, it had no effect on the growth of several mammalian cells. In conclusion, we isolated nornidulin from Indonesian <i>Aspergillus</i> sp. BioMCC f.T.8501 as a novel inhibitor of <i>Pf</i>MQO, which showed inhibitory activity against the proliferation of <i>P. falciparum</i> 3D7 in vitro.