3-alkyl- and 3-aryl-(7-oxo-7H-furo[3, 2-g]chromen-5-yl)alkanoic acids as inhibitors of leukotriene B4 biosynthesis.
The synthesis and biological properties of 3-alkyl-and 3-aryl-(7-oxo-7H-furo [3, 2-g]chromen-5-yl)alkanoic acids are described. The compounds were evaluated for their ability to inhibit soybean 15-lipoxygenase (15-LO) and the production of leukotriene B(4) (LTB(4)) in bovine polymorphonuclear leukocytes. The furocoumarins were further investigated for their lipophilicity and their capacity to photobleach N, N-dimethyl-p-nitrosoaniline (RNO) after irradiation with UVA light. The synthesised furocoumarins showed only a moderate ability to inhibit the 15-LO and the production of LT B(4). The 3-alkyl substituted furocoumarins had a higher capacity to photobleach RNO than then the 3-aryl substituted furocoumarinso. The inhibitory activity of the newcompounds was quite modest in comparison to other known inhibitors of 15-LO and LTB(4) production. Nevertheless, they may provide the basis for the development of more potent antiinflammatory potential photoreactive furocoumarins.
Körner
Paul
P
Pharmazeutisches Institut, Universität Kiel, Germany. pKoerner@pharmazie.uni-kiel.de
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002417:Cattle; D015195:Drug Design; D011564:Furocoumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016859:Lipoxygenase Inhibitors; D009682:Magnetic Resonance Spectroscopy; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009603:Nitroso Compounds / Q000737:chemistry / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013025:Glycine max; D014466:Ultraviolet Rays
D000893:Anti-Inflammatory Agents; D011564:Furocoumarins; D016859:Lipoxygenase Inhibitors; D009603:Nitroso Compounds; D017319:Photosensitizing Agents; C008651:4-nitrosodimethylaniline; D007975:Leukotriene B4