期刊
JOURNAL OF NATURAL PRODUCTS
卷 85, 期 5, 页码 1442-1447出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.1c01060
关键词
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资金
- NSFC [81991524, 82174089]
- National Key R&D Program of China [2018YFC1706200]
- Jiangsu Qing-lan Project
A new antiosteoporotic compound, Spirocitromycetin, has been characterized and its structure and biosynthetic pathway have been elucidated. Furthermore, a novel antiosteoporotic pharmacophore has been identified.
Spirocitromycetin, an antiosteoporotic polyketide bearing a unique spirocycle, was characterized from a human mucus sputum-derived Penicillium velutinum. Its structure and absolute configuration were elucidated spectrally, with its biosynthetic pathway likely mediated via polivione, a reported heptaketide. Spirocitromycetin was shown to be antiosteoporotic at 0.1 mu M in the prednisolone-induced osteoporotic zebrafish model. A combination of spirocitromycetin variant synthesis and bioassay has identified 5 '-methyl-3 ' H-spiro[chromane-3,2 '-furan]- 3 ',4-dione as an unreported antiosteroporotic pharmacophore. Collectively, this work offers new starting (sub)structures that may be of significance for antiosteoporotic drug discovery
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