Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94
Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94
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DOI：
10.1021/acs.jnatprod.1c00677
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发表时间：
2021-12-24
影响因子：
5.1
通讯作者：
Osada, Hiroyuki
中科院分区：
文献类型：
--
作者：
Abdelhakim, Islam A.;Bin Mahmud, Fauze;Osada, Hiroyuki
利用新近发现的次生代谢调节剂NPD 938来改变镰刀菌RK 97 -94的次生代谢产物谱。通过UPLC-ESI-MS分析在NPD 938处理的培养物中检测到三种Lucilactaene类似物。通过广泛的光谱分析，成功纯化并鉴定了三种代谢产物，分别为二氢NG 391（1）、二氢Lucilactaene（2）和13 α-羟基Lucilactaene（3）。二氢NG 391（1）显示出弱的体外抗疟活性（IC 50 = 62 μ M）。相反，二氢Lucilactaene（2）和13 α-羟基Lucilactaene（3）显示出非常有效的抗疟活性（IC 50分别为0.0015和0.68 μ M）。这些研究结果提供了洞察的结构-活性关系的光泽乳烯及其类似物作为抗疟疾的先导化合物。
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 13 alpha-hydroxylucilactaene (3) via extensive spectroscopic analyses. DihydroNG391 (1) exhibited weak in vitro antimalarial activity (IC50 = 62 mu M). In contrast, dihydrolucilactaene (2) and 13 alpha-hydroxylucilactaene (3) showed very potent antimalarial activity (IC50 = 0.0015 and 0.68 mu M, respectively). These findings provide insight into the structure-activity relationship of lucilactaene and its analogues as antimalarial lead compounds.