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

  • J Nat Prod. 2022 Jan 28;85(1):63-69. doi: 10.1021/acs.jnatprod.1c00677.
Islam A Abdelhakim  1  2  3  4 ,  Fauze Bin Mahmud  3  5  6 ,  Takayuki Motoyama  3 ,  Yushi Futamura  3 ,  Shunji Takahashi  4 ,  Hiroyuki Osada  3
Affiliations
  • 1. Graduate School of Science and Engineering, Saitama University, Sakura, Saitama 338-8570, Japan.
  • 2. Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt.
  • 3. Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama 351-0198, Japan.
  • 4. Natural Product Biosynthesis Research Unit, RIKEN CSRS, Wako, Saitama 351-0198, Japan.
  • 5. Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang 11800, Malaysia.
  • 6. Faculty of Science and Natural Resources, Universiti Malaysia Sabah, Sabah 88400, Malaysia.
PMID: 34949088 DOI: 10.1021/acs.jnatprod.1c00677
Abstract

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 (IC50 = 62 μM). In contrast, dihydrolucilactaene (2) and 13α-hydroxylucilactaene (3) showed very potent antimalarial activity (IC50 = 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.