Tandocyclinones A and B, Ether Bridged <i>C</i>-Glycosyl Benz[<i>a</i>]anthracenes from an Intertidal Zone <i>Streptomyces</i> sp.
Thanh-Hau Huynh,
Eun Seo Bae,
Bo Eun Heo,
Jayho Lee,
Joon Soo An,
Yun Kwon,
Sang-Jip Nam,
Ki-Bong Oh,
Jichan Jang,
Sang Kook Lee,
Dong-Chan Oh
Affiliations
Thanh-Hau Huynh
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Eun Seo Bae
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Bo Eun Heo
Division of Life Science, Department of Bio & Medical Big Data (BK21 Four Program), Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
Jayho Lee
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea
Joon Soo An
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Yun Kwon
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea
Sang-Jip Nam
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea
Ki-Bong Oh
Department of Agricultural Biotechnology, College of Agriculture and Life Sciences and Natural Products Research Institute, Seoul National University, Seoul 08826, Republic of Korea
Jichan Jang
Division of Life Science, Department of Bio & Medical Big Data (BK21 Four Program), Research Institute of Life Science, Gyeongsang National University, Jinju 52828, Republic of Korea
Sang Kook Lee
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
Dong-Chan Oh
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
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)-d8 selected after an extensive search for a solvent, resulting in mostly observable exchangeable protons in the 1H 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 Mo2(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 (MIC50 = 40.8 μM) and antiproliferative activity against SNU638 and HCT116 cancer cells, with IC50 values of 31.9 µM and 49.4 µM, respectively.
