Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94.

A recently discovered secondary metabolism regulator, NPD938, was used to alter the secondary metabolite profile in Fusarium sp. RK97-94. Three lucilactaene analogues were detected via UPLC-ESI-MS analysis in NPD938-treated culture. The three metabolites were successfully purified and identified as dihydroNG391 ( 1 ), dihydrolucilactaene ( 2 ), and 13α-hydroxylucilactaene ( 3 ) via extensive spectroscopic analyses. DihydroNG391 ( 1 ) exhibited weak in vitro antimalarial activity (IC 50 = 62 μM). In contrast, dihydrolucilactaene ( 2 ) and 13α-hydroxylucilactaene ( 3 ) showed very potent antimalarial activity (IC 50 = 0.0015 and 0.68 μM, respectively). These findings provide insight into the structure-activity relationship of lucilactaene and its analogues as antimalarial lead compounds.