Nakamusines A−C, new 9-methyladeninium diterpenoid alkaloids from a Formosan marine sponge Agelas nakamurai

Abstract

Three new 9-methyladeninium diterpenoids, nakamusines A−C (1−3), along with four known analogous metabolites and a precursor of them were isolated from the Taiwanese sponge Agelas nakamurai. These new chemical structures were determined by extensive spectroscopic analysis, particularly HRESIMS and NMR data. The absolute configuration of nakamusine A (1) was deduced by the experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra, is the 9-methyladeninium diterpenoid with a different configuration from the genus Agelas. Furthermore, 9-methyladenine (8) was isolated from Agelas sponge in this study, proving it to be an imperative precursor for the biosynthesis of 9-methyladeninium diterpenoids in Agelas sponge. The in vitro cytotoxicity, and antibacterial activity of these sponge natural products were also evaluated. Notably, (−)-agelasine C (4) and (−)-agelasine D (5) inhibited the growth of the microbial pathogen, Neisseria gonorrhoeae. Moreover, 4 and 5 showed cytotoxicity toward the human breast adenocarcinoma (MDA-MB-231) and oral squamous cell carcinoma (Ca9-22) with IC50 values of 37.4 and 12.1 μM, respectively.