Precursor-Directed Generation of Indolocarbazoles with Topoisomerase IIα Inhibitory Activity

Marine Drugs
Cong WangWeiming Zhu

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.

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Citations

Feb 7, 2020·Natural Product Reports·Anthony R CarrollMichèle R Prinsep
Feb 1, 2020·Recent Patents on Anti-cancer Drug Discovery·Hongyu TaoXiukun Lin
May 29, 2020·Journal of Natural Products·Julia MoschnyTimo H J Niedermeyer
Sep 7, 2021·Archiv der Pharmazie·Feng SongDi Qiu

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Methods Mentioned

BETA
NMR
electron-capture
column chromatography
fluorescence activated cell sorting
flow cytometry
electrophoresis

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis