Precursor-Directed Generation of Indolocarbazoles with Topoisomerase IIα Inhibitory Activity

Cong Wang; Adeep Monger; Liping Wang; Peng Fu; Pawinee Piyachaturawat; Arthit Chairoungdua; Weiming Zhu

doi:10.3390/md16050168

Marine Drugs (May 2018)

Precursor-Directed Generation of Indolocarbazoles with Topoisomerase IIα Inhibitory Activity

Cong Wang,
Adeep Monger,
Liping Wang,
Peng Fu,
Pawinee Piyachaturawat,
Arthit Chairoungdua,
Weiming Zhu

Affiliations

Cong Wang: Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Adeep Monger: Toxicology Graduate Program, Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Liping Wang: Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang 550002, China
Peng Fu: Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
Pawinee Piyachaturawat: Toxicology Graduate Program, Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Arthit Chairoungdua: Toxicology Graduate Program, Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Weiming Zhu: Key Laboratory of Marine Drugs, Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China

DOI: https://doi.org/10.3390/md16050168
Journal volume & issue: Vol. 16, no. 5
p. 168

Abstract

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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.

Published in Marine Drugs

ISSN: 1660-3397 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/marinedrugs

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