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Indimicins A-E, Bisindole Alkaloids from the Deep-Sea-Derived Streptomyces sp. SCSIO 03032

Significance Statement

Bisindole alkaloids are a large family of natural products with pharmaceutical significance. Several analogues have been advancing into clinic trials in development as protein kinase inhibitors or DNA-topoisomerase I inhibitors. Although more than 300 analogues of bisindole alkaloids have been reported, new members of this family of natural products are continually discovered or generated contingent upon isolation from natural sources, synthesis and metagenomic screening. In the past two decades, the documentation of marine actinomycetes as a new source for novel natural products has inspired great efforts in accessing and exploiting the vast ocean for potential “blue tablets”. In this study, we showed that the deep-sea derived Streptomyces sp. SCSIO 03032 was capable of producing indimicins A–E (1–5), which are bisindole alkaloids bearing an unprecedented 1′,3′-dimethyl-2′-hydroindole moiety, in addition to spiroindimicins with novel 5,5 or 5,6 spiro-ring scaffolds produced by the same strain (Org. Lett., 2012, 3364). The C-methylation at a quandary carbon C-3′ led to a dearomatized indolocarbazole scaffold in 1–4. Also, the C-methylation at C-2 of the pyrrole moiety in 2 and 3 has never been reported for this family of natural products. Indimicin B (2) showed moderate cytotoxic activities toward MCF-7. These new structure expand the chemical entity of indole alkaloids and provide challenges to investigate their biosynthetic origins at genetic and biochemical levels, and should bring opportunities for screening of their new biological activities.

 

Indimicins A-E, Bisindole Alkaloids from the Deep-Sea-Derived Streptomyces sp. SCSIO 03032

Journal Reference

Zhang W , Ma L , Li S, Liu Z , Chen Y§, Zhang H, Zhang G , Zhang Q, Tian X , Yuan C, Zhang S , Zhang W §, and Zhang C *. J Nat Prod. 2014: 77 (8), pp 1887–1892.
Show Affiliations
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, RNAM Center for Marine Microbiology, Guangdong Key Laboratory of Marine Materia Medica, Collaborative Innovation Center of Deep Sea Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, People’s Republic of China
Guangzhoujinan Biomedicine Research and Development Center, Guangdong Key Laboratory of Bioengineering Medicine, Jinan University, 601 West Huangpu Road, Guangzhou 510632, People’s Republic of China
§ Guangdong Institute of Microbiology, 100 Central Xianlie Road, Guangzhou 510070,People’s Republic of China.

Abstract

Five new bisindole alkaloids, indimicins A-E (15), bearing a unique 1′,3′-dimethyl-2′-hydroindole moiety, were isolated from the marine-derived Streptomyces sp. SCSIO 03032, along with two new compounds, lynamicins F and G (6 and 7). Their planar structures were elucidated by detailed interpretation of their MS and NMR spectroscopic data, and the absolute configurations were determined by X-ray crystallographic analysis (for 1), comparison of CD spectra (for 24), and quantum chemical calculations (for 5). Indimicin B (2) exhibited moderate cytotoxic activity toward the MCF-7 cell line.

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