Precursor-Directed Generation of Indolocarbazoles with Topoisomerase IIα Inhibitory Activity

Abstract

One new indolocarbazole, 3-hydroxy-K252d (<b>3</b>), together with the recently reported 3-hydroxyholyrine A (<b>1</b>) and 3'-<i>N</i>-acetyl-3-hydroxyholyrine A (<b>2</b>), were obtained by feeding a culture of the marine-derived <i>Streptomyces</i> strain OUCMDZ-3118 with 5-hydroxy-l-tryptophan. Their structures were elucidated on the basis of spectroscopic analysis. Compound <b>1</b> potently induced apoptosis of gastric cancer cells by inhibiting topoisomerase IIα enzyme activity and reducing the expression of antiapoptosis protein level. Compound <b>3</b> displayed moderate cytotoxicity against the A549 and MCF-7 cell lines with IC₅₀ values of 1.2 ± 0.05 μM, 1.6 ± 0.09 μM, respectively.