Abstract
A screening of our actinomycete fraction library against the NCI-60 SKOV3 human tumor cell line led to the isolation of isopimara-2-one-3-ol-8,15-diene (1), lagumycin B (2), dehydrorabelomycin (3), phenanthroviridone (4), and WS-5995 A (5). These secondary metabolites were produced by a Micromonospora sp. isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam. Compound 1 is a novel Δ8,9-pimarane diterpene, representing one of approximately 20 actinomycete-produced diterpenes reported to date, while compound 2 is an angucycline antibiotic that has yet to receive formal characterization. The structures of 1 and 2 were elucidated by combined NMR and MS analysis and the absolute configuration of 1 was assigned by analysis of NOESY NMR and CD spectroscopic data. Compounds 2–5 exhibited varying degrees of cytotoxicity against a panel of cancerous and non-cancerous cell lines. Overall, this study highlights our collaborative efforts to discover novel biologically active molecules from the large, underexplored, and biodiversity-rich waters of Vietnam’s East Sea.
Highlights
Natural products and their synthetic derivatives are essential toward the discovery of drugs, accounting for greater than 74% of marketed small molecule therapies [1,2]
Through an in vitro growth inhibition screening of our fraction library against the NCI-60 SKOV3 human tumor cell line, we identified an actinomycete isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam
Since a previous report that mined the genomes of a small population of actinomycete strains suggested that this phylum has a far greater capacity to produce diterpenes (25 of 100 strains) than is represented in the peer reviewed literature, it is possible that this discrepancy is a product of these pathways remaining silent under laboratory growth conditions, or of the methods used to isolate natural products from bacteria, namely bioassay-guided fractionation [3]
Summary
Natural products and their synthetic derivatives are essential toward the discovery of drugs, accounting for greater than 74% of marketed small molecule therapies [1,2]. Through an in vitro growth inhibition screening of our fraction library against the NCI-60 SKOV3 human tumor cell line, we identified an actinomycete isolated from sediment collected off the Cát Bà peninsula in the East Sea of Vietnam. From this strain we isolated and characterized the novel diterpene isopimara-2-one-3-ol-8,15-diene (1) and lagumycin B (2), an angucycline that has yet to receive full structural characterization in the peer-reviewed literature (Figure 1) [7]. We present the structure elucidation and biological activity of these compounds
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