1-Hydroxy-1-Norresistoflavins B and C, resistomycin-type polyketides from the Marine-Derived Streptomyces althioticus 2304JJ-041.

Two new resistomycin-type pentacyclic polyketide derivatives, designated 1-hydroxy-1-norresistoflavins B (1) and C (2), together with 1R-hydroxy-1-norresistomycin (3) and (6 R)-6,11-Dihydro-7-hydroxy-6-(hydroxymethyl)-8-methoxy-3,9-dimethyl-4H-pyrazino[1,2-b]isoquinolin-4-one (4), were isolated from the marine-derived actinomycete Streptomyces althioticus. Their structures were elucidated by comprehensive spectroscopic analyses, including 1D and 2D NMR and HR-ESIMS data, and the absolute configurations were determined by comparison with experimental and calculated electronic circular dichroism (ECD) spectra. In addition, the absolute configuration of 3 was experimentally determined for the first time based on its ECD data. All isolated compounds were evaluated for cytotoxicity against a panel of six solid cancer cell lines and seven blood cancer cell lines. Compound 3 exhibited significant cytotoxicity against several blood cancer cell lines, with GI50 values ranging from 0.33 to 1.24 μM, and moderate activity against solid cancer cell lines with GI50 values of 6.67 - 10.16 μM. Compounds 1 and 2 exhibited weak to moderate cytotoxicity against some blood cancer cell lines, with GI50 values of 8.89 - 24.53 μM and 10.68 - 22.88 μM, respectively, and showed weak activity against solid cancer cell lines.