title: Syntheses and evaluation of the antioxidant activity of novel methoxypsoralen derivatives.
abstract: A series of 5- and 8-methoxypsoralen (MOP) analogs, suitable for structure-antioxidative/anti-inflammatory activity relationship studies, were synthesized using as key-reactions the selective monobromination of MOPs with N-bromosaccharin and either a Heck reaction or a Suzuki coupling or a Suzuki coupling followed by a Wittig reaction to install side-chains of the acrylate- or benzoate- or cinnamate-type, respectively. The 8-MOP analogs 19 and 24, incorporating at position 5 of the psoralen nucleus a butyl acrylate or a tert-butyl cinnamate moiety, were the most powerful inhibitors of soybean LOX and inhibited effectively lipid peroxidation. Analog 19 was a more potent anti-inflammatory agent than the reference compound indomethacin and of comparable cytocompatibility to 8-MOP whereas analog 24 was a weaker inhibitor of inflammation than indomethacin and significantly more cytotoxic than 8-MOP. The results of the biological tests are discussed in terms of structural characteristics.
authors.affiliation: Laboratory of Synthetic Organic Chemistry, Department of Chemistry, School of Natural Sciences, University of Patras, 26504 Patras, Greece.
authors.forename: Stavros E
authors.initials: SE
authors.lastname: Bariamis
authors.forename: Marilena
authors.initials: M
authors.lastname: Marin
authors.forename: Constantinos M
authors.initials: CM
authors.lastname: Athanassopoulos
authors.forename: Christos
authors.initials: C
authors.lastname: Kontogiorgis
authors.forename: Zinovia
authors.initials: Z
authors.lastname: Tsimali
authors.forename: Dionissios
authors.initials: D
authors.lastname: Papaioannou
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sindona
authors.forename: Giovanni
authors.initials: G
authors.lastname: Romeo
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Avgoustakis
authors.forename: Dimitra
authors.initials: D
authors.lastname: Hadjipavlou-Litina
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008084:Lipoxygenase / Q000378:metabolism*; D015394:Molecular Structure; D013025:Glycine max / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D011564:Furocoumarins; D008084:Lipoxygenase