The bacteria of the genus Streptomyces are prolific microorganisms for their production of intriguing secondary metabolites. Of them, most are pharmaceutically important natural products with different biological activities, including antimicrobial, antimalarial, cytotoxic and antitumor properties. The immense diversity of Streptomyces, along with its under-utilization is another fundamental reason for attracting researchers to discover novel secondary metabolites.
Prof. Luo yinggang’s group of Chengdu Institute of Biology, Chinese Academy of Sciences has long been committed to isolating and characterizing the intriguing secondary metabolites of plants and microorganisms. There has been increasing number of novel metabolites isolated and characterized by Prof. Luo from different biogenetic resources with different biological activities.
Inspired by the impressive pharmaceutical potent of the secondary metabolites from Streptomyces, a program aiming at the discovery of new antitumor chemical entities from Streptomyces was initiated. Fermentation broth extract of strain Streptomyces spp. CIBYL1 was found to be active (GI50 = 40 μg/mL) against human hepatic cancer cells HepG2.
Thus bioassay-guided chemical investigations on this extract by successive silica gel column chromatography afforded a novel secondary metabolite which containing three moieties, cinnamoyl group, 2-amino oxazole and 1,2-disubstituted cyclododecane, named N-trans-cinnamoyl 2-amino-3a,4,5,6,7,8,9,10,11,12,13,13a-dodecahydrocyclododeca[d]oxazol, along with five known compounds, pimprinine, (3R,4S,5R,6R)-3,4,5,6-tetrahydro-4-hydroxy- 3,5,6-trimethyl-2H-pyran-2-one, 15 indolyl-3-carboxylic acid, 2-phenylacetamide and di(1H-pyrrol-2-yl)methanone.
The structures of these metabolites were elucidated on the basis of extensive analysis of spectroscopic data, including OR, IR, HRMS, 1D and 2D NMR data and chemical derivation. Among them, pimprinine displayed promising anticonvulsant activity in both minimum and maximum electric seizure threshold test in mice.
The paper entitled "A new cyclododeca[d]oxazole derivative from Streptomyces spp. CIBYL1" has been formally published on Natural Product Research (2013, 27, 603-608).