We have been investigating cytotoxic secondary with excellent solid tumor selectivity from marine-derived actinomycetes. For rapid identification of solid tumor selective compounds and their mode of action, an extract library of actinomycetes have been applied to two kinds of cytotoxic screening systems, HeLa cell-based cytological profiling (CP) and anticancer disk diffusion assay (DDA). The organic extract of the Stereptomycessp. CP55-76 separated from deep-water sediment (-900 m) collected in Santa Monica Basin showed significant cytotoxic effect against HeLa cells and selective cytotoxicity against the human prostate adenocarcinoma cell line (LNCaP), identified by CP and DDA, respectively. Initial investigation of the secondary metabolites produced by this strain led to isolation of a new meroterpenoids 1together with three known meroterpenoinds 2– 4 from the 80% MeOH in H2O of the reversed-phase flash column chromatography. In this study, we have conducted a scale-up culture (90 L) for detailed analysis of LNCaP selective cytotoxic compounds from the strain CP55-76. A combination of CP-DDA approach-based isolation and molecular networking analysis has identified additional two new meroterpenoinds 5 and 6 from 80% and 4% MeOH in H2O flash column chromatography fractions, respectively. The structures of the new compounds were elucidated based on comprehensive 1D and 2D NMR analysis. The details of structure elucidation of 5 and 6 and cytotoxic effects of the isolated compounds will be presented.

Two new meroterpenoids produced by the deep-water sediment-derived Streptomyces sp. CP55-76

ACS Fall 2020 Virtual Meeting

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