Tandocyclinones A and B, Ether Bridged C -Glycosyl Benz[ a ]anthracenes from an Intertidal Zone Streptomyces sp.

Two new proton-deficient metabolites, tandocyclinones A and B ( 1 and 2 ), were discovered via the chemical profiling of the Streptomyces sp. strain TDH03, which was isolated from a marine sediment sample collected from the intertidal mudflat in Tando Port, the Republic of Korea. The structures of 1 and 2 were elucidated as new ether-bridged C -glycosyl benz[ a ]anthracenes by using a combination of spectroscopic analyses of ultraviolet (UV) and mass spectrometry (MS) data, along with nuclear magnetic resonance (NMR) spectra, which were acquired in tetrahydrofuran (THF)- d ₈ selected after an extensive search for a solvent, resulting in mostly observable exchangeable protons in the ¹ H NMR spectrum. Their configurations were successfully assigned by applying a J -based configuration analysis, rotating-frame Overhauser enhancement spectroscopy (ROESY) NMR correlations, chemical derivatization methods based on NMR (a modified version of Mosher's method) and circular dichroism (CD) (Snatzke's method using Mo ₂ (OAc) ₄ -induced CD), as well as quantum-mechanics-based computational methods, to calculate the electronic circular dichroism (ECD). Tandocyclinones A and B ( 1 and 2 ) were found to have weak antifungal activity against Trichophyton mentagrophytes IFM40996 with an MIC value of 128 μg/mL (244 and 265 μM for 1 and 2 , respectively). A further biological evaluation revealed that tandocyclinone A ( 1 ) displayed inhibitory activity against Mycobacterium avium (MIC ₅₀ = 40.8 μM) and antiproliferative activity against SNU638 and HCT116 cancer cells, with IC ₅₀ values of 31.9 µM and 49.4 µM, respectively.