Anti-Cancer Agents in Medicinal Chemistry

(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Michelle Prudhomme  
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France

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PreQ0 Base, an Unusual Metabolite with Anti-cancer Activity from Streptomyces qinglanensis 172205

Author(s): Dongbo Xu, Min Ma, Yongfeng Liu, Ting Zhou, Kexin Wang, Zixin Deng, Kui Hong.

Graphical Abstract:


Abstract:

PreQ0 base (7-cyano-7-deazaguanine, compound 1) is the biosynthetic precursor of queuosine-tRNA and important synthetic intermediate for bioactive compounds. It was obtained for the first time as a new natural product from a mangrove actinomycete Streptomyces qinglanensis 172205, during the course of searching for anti-cancer compounds from marine microbes. PreQ0 base showed anti-HeLa (IC50 = 62.0 μg/ml) and anti-HepG2 (IC50 = 80.6 μg/ml) activities, higher cytotoxicity than the positive control, fluorouracil. Furthermore, it exhibited weak α -glucosidase inhibitory activity, but no obvious antimicrobial and Aβ1-42 fibrillation inhibitory activities. In silico analysis of the genome of the strain 172205 revealed a putative biosynthetic gene cluster directing the biosynthesis of PreQ0 base. The gene cluster only contained three Open Reading Frames (ORFs), queC, queD and queE. The absence of the key gene queF encoding 7-cyano-7-deazaguanine reductase catalyzing PreQ0 base to PreQ1 base suggested that the strain only has the capacity of accumulation of PreQ0 base as a metabolite, consistent with our observation in chemical identification.

Keywords: Anti-cancer, biosynthetic gene cluster, mangrove actinomycete, natural product, PreQ0 base.

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Article Details

VOLUME: 15
ISSUE: 3
Year: 2015
Page: [285 - 290]
Pages: 6
DOI: 10.2174/1871520614666141027144653
Price: $58