Precursor-Directed Generation of Indolocarbazoles with Topoisomerase IIα Inhibitory Activity

Abstract

One new indolocarbazole, 3-hydroxy-K252d (3), together with the recently reported 3-hydroxyholyrine A (1) and 3′-N-acetyl-3-hydroxyholyrine A (2), were obtained by feeding a culture of the marine-derived Streptomyces strain OUCMDZ-3118 with 5-hydroxy-l-tryptophan. Their structures were elucidated on the basis of spectroscopic analysis. Compound 1 potently induced apoptosis of gastric cancer cells by inhibiting topoisomerase IIα enzyme activity and reducing the expression of antiapoptosis protein level. Compound 3 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.

Advances in Biosynthesis of Natural Products from Marine Microorganisms

“…This class of NPs have been found in many species, including fungi, invertebrates, and terrestrial and marine actinomyces, and have strong physiological activities and interesting chemical structures [91]. One new ICZ, 3-hydroxy-K252d 17 (Figure 6), was obtained by feeding a culture of the marine Streptomyces strain OUCMDZ-3118 with a precursor 5-hydroxy-L-tryptophan, along with previously reported compounds 3-hydroxyholyrine A 15 and 3 -N-acetyl-3-hydroxyholyrine A 16 [92]. The structure of 17 was confirmed by 2D NMR correlations.…”

“…The identity of the sugar moiety was determined to be l-rhamnose by gas chromatography-mass spectrometry (GC-MS) analysis of the acid hydrolysate of 17. Cytotoxicity tests showed that 17 had moderate toxicity against the human lung cancer cell line A549 and the human breast cancer cell line MCF-7, with IC 50 values of 1.2 µM and 1.6 µM, respectively [92].…”

“…Chemical structures of hydroxy-substituted indolocarbazoles 15-17 obtained by feeding a precursor 5-hydroxy-L-tryptophan to the marine Streptomyces strain OUCMDZ-3118. The IC 50 values of these products against the A549 (human lung adenocarcinoma), K562 (human erythroleukemia), and MCF-7 cell lines are also given [92]. Reproduced with permission from [92].…”

The anticancer activity of carbazole alkaloids

“…3-Hydroxyholyrine A (13, IC 50 : 0.51-7.2 µM, MTT assay), obtained by feeding a culture of the marine-derived Streptomyces strain OUCMDZ-3118 with 5-hydroxy-tryptophan, possessed broadspectrum activity against A549, MCF-7, K562, AGS, and MKN45 cancer cell lines. [50] The mechanistic investigations illustrated that 3-hydroxyholyrine A potently induced apoptosis of gastric cancer cells by inhibiting topoisomerase IIα enzyme activity and reducing the expression of antiapoptosis protein level.…”

New Ansamycins from the Deep-Sea-Derived Bacterium Ochrobactrum sp. OUCMDZ-2164

“…As part of our studies to search for new bioactive NPs from deep-sea-derived bacteria [ 33 , 34 , 35 ], we found that the extract of the fermentation broth of a deep-sea (2000 m) water-derived Ochrobactrum sp. OUCMDZ-2164 showed cytotoxic effect on the A549 (83% inhibition) and K562 (70% inhibition) cell line at 0.1 mg/mL.…”