sorbicillin and sorbicillinol

Recently, we demonstrated potential anti-inflammatory effects of sorbicillinoids isolated from marine fungi. Here, we report the synthesis of a series of new sorbicillinoid analogues and assessed their anti-inflammatory activities. Our results reveal that side chain substitution with (E)-2-butenoyl, (E)-3-(4-fluorophenyl)-2-propenoyl, and (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoyl significantly enhanced the inhibitory effects of the derivatives on nitric oxide (NO) production and inducible NO synthesis (iNOS) expression stimulated by lipopolysaccharides (LPS) in mouse macrophage. Further chemical derivatization shows that the monomethylresorcinol skeleton worked better than the dimethylresorcinol skeleton in inhibiting LPS-induced inflammatory response in cultured cells. Among the 29 synthesized sorbicillinoid analogues, compounds 4b and 12b exhibited the strongest anti-inflammatory activities, holding the promise of being developed into lead compounds that can be explored as potent anti-inflammation agents.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Products; Cell Survival; Cells, Cultured; Cyclohexanones; Dose-Response Relationship, Drug; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Structure-Activity Relationship

In our screening of microorganisms for new natural products, the fungus Penicillium notatum delivered further members of the sorbicillin family, namely, the sohirnones A [3, 1-(2,4-dihydroxy-5-methylphenyl)hex-4-en-1-one], B [4a, 1-(2,4,5-trihydroxy-3,6-dimethylphenyl)hexa-2,4-dien-1-one], and C [5, 1-(2,4,5-trihydroxy-3,6-dimethylphenyl)hex-4-en-1-one]. A stable tautomer of oxosorbicillinol (7) was characterized as 6, and the recently described 7-deacetoxyyanuthone (8) was reisolated. The additionally isolated rezishanones A-D (12-13c) are the first natural Diels-Alder products of sorbicillinol (1) with dienophiles not related with 1. The monomers and dimers showed weak antibacterial activity, but were inactive against fungi and algae. The structures were determined by spectroscopic methods and by comparison of the NMR data with those of the structurally related 2',3'-dihydrosorbicillin (2) and, in the case of 4a, by transformation into the known sorrentanone (4b).

Topics: Anti-Bacterial Agents; Cyclohexanones; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Penicillium chrysogenum; Resorcinols

An incorporation study of [1-(13)C] and [1,2-(13)C2] labeled sodium acetates into sorbicillinol 1 established a ring closure system between C-1 and C-6 and the positions that were oxidized and/or methylated on a hexaketide chain. Subsequent investigations, using 13C-labeled 1 prepared from [1-(13)C] labeled sodium acetate, clearly demonstrated that both bisorbicillinol 2 and sorbicillin 6 incorporated 13C-labeled 1 into their carbon skeletons. 13C-labeled bisorbicillinols 2 derived from [1-(13)C]- and [2-(13)C]-labeled sodium acetates clearly indicate that these were on the biosynthetic route from 1 to bisorbibutenolide (bislongiquinolide) 3 and bisorbicillinolide 4 via 2 as a branching point in the fungus.

Topics: 4-Butyrolactone; Acetylation; Bridged Bicyclo Compounds; Bridged-Ring Compounds; Cyclohexanones; Fermentation; Magnetic Resonance Spectroscopy; Models, Molecular; Resorcinols; Trichoderma