Microbial transformation of deoxyandrographolide and their inhibitory activity on LPS-induced NO production in RAW 264.7 macrophages

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 4; pp. 1615 - 1618
• Main Authors: Deng, Sa, Zhang, Bao Jing, Wang, Chang Yuan, Tian, Yan, Yao, Ji Hong, An, Lei, Huang, Shan Shan, Peng, Jin Yong, Liu, Ke Xin, Ma, Xiao Chi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.02.2012; Elsevier
• Subjects: Biological and medical sciences; Biotransformation; Cunninghamella; Cunninghamella - enzymology; Cunninghamella - metabolism; Deoxyandrographolide; Diterpenes - chemistry; Diterpenes - metabolism; Diterpenes - pharmacology; Ent-labdane; Lipopolysaccharides; Macrophages; Macrophages - drug effects; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Structure; N.M.R; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; NO inhibition; nuclear magnetic resonance spectroscopy; Pharmacology. Drug treatments; Structure-Activity Relationship; Structure-activity relationships; Transformation; Deoxyandrographolide; Ent-labdane; NO inhibition; Biotransformation; Terpenoid; Monocyte; Rodentia; Chemical structure; Biological activity; Vertebrata; Mammalia; Cell line; Mouse; Animal; Production; Diterpene; Inhibition; Labdane derivatives; Macrophage
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.12.122

A series of analogues of deoxyandrographolide (1) transformed by Cunninghamella blakesleana AS 3.2004 were isolated and identified by spectral methods including 2D NMR. Among them, 3-oxo-17,19-dihydroxy-7,13-ent-labdadien-15,16-olide (9), 3-oxo-19-hydroxy-1,13-ent-labdadien-15,16-olide (16), 3-oxo-1β-hydroxy-14-deoxy-andrographolide (17) and 3-oxo-2β-hydroxy-14-deoxyandrographolide (18) are new compounds. And their structure–activity relationships (SAR) of inhibitory activity on LPS-induced NO production in RAW 264.7 macrophage cells were also discussed.