title: Pruinosanones A-C, anti-inflammatory isoflavone derivatives from Caragana pruinosa.
abstract: Pruinosanone A (1), a novel spirochromone, was isolated from the roots of Caragana pruinosa. Two biogenetically related isoflavone intermediates, pruinosanones B and C (2 and 3), were also isolated, together with five known analogs identified as 3-hydroxy-9-methoxypterocarpan (4), 7,2'-dihydroxy-4'-methoxyisoflavanol (5), retusin-8-methylether (6), 7,2'-dihydroxy-8,4'-dimethoxy isoflavone (7) and 7,3'-dihydroxy-8,4'-dimethoxy isoflavone (8). The structures of 1-3 were elucidated based on extensive spectroscopic methods. Notably, 1 is the first example of a spirochromone possessing an unprecedented pentacyclic skeleton containing a spiro[benzo[d][1,3]dioxole-2,3'-chroman]-4'-one motif, which was confirmed by X-ray diffraction analysis. A plausible biosynthetic pathway for 1 was also proposed. Compounds 1-8 were tested for their ability to inhibit nitric oxide (NO) production in LPS-induced RAW 264.7 macrophages, and compounds 1-3 were the most potent inhibitors of NO production, with IC50 values of 1.96, 1.93 and 1.58 μM, respectively. A structure-activity relationship analysis revealed that the fused 2-isopropenyl-2,3-dihydrofuran moiety plays a vital role in the potency of these compounds. Moreover, 1 was found to significantly inhibit inducible nitric oxide synthase (iNOS) protein expression, which accounts for the potent inhibition of NO production by this spirochromone.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chengjian
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Xin
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Xinjiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi 830002, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Pan
authors.affiliation: Xinjiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi 830002, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Luping
authors.initials: L
authors.lastname: Qin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D032602:Caragana / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018517:Plant Roots / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D000893:Anti-Inflammatory Agents; D007529:Isoflavones; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II