Cuevaenes F-H, Including Two Rare Chlorinated Cuevaenes From the Marine-Derived Streptomyces malaysiensis HNM0561

Three new cuevaenes, designated cuevaenes F-H (1-3), together with four known analogues (4-7), were isolated from the marine-derived strain Streptomyces malaysiensis HNM0561. Their structures and absolute configurations were elucidated using HR-ESIMS, extensive 1D and 2D NMR spectroscopy, and ECD calculations. Notably, this study establishes the absolute configurations of previously reported cuevaenes (4, 5, and 7) for the first time. Compounds 1 and 2 are distinguished by a rare chlorine substitution at C-17, representing a novel structural motif within the cuevaene family. Additionally, compounds 1-6 were derivatized via esterification with (trimethylsilyl)diazomethane (TMSCHN₂) to afford the corresponding methyl esters (1a-6a). All isolated and derivatized compounds (1-7 and 1a-6a) were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV2 microglial cells. Among them, compounds 3 and 4a exhibited significant inhibitory activity, reducing NO production by 54% and 47% at a concentration of 20 µM, respectively.