- Free Radical Oxidation of (E)-Retinoic Acid by Prostaglandin H Synthase
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Cooxidative metabolism of all-trans (E)-retinoic acid (RA) by prostaglandin H synthase was investigated employing ram seminal vesicle microsomes (RSVM) or purified, RSVM-derived enzyme. RA was shown to undergo hydroperoxide [H2O2 or 5-phenyl-4-penten-1-yl hydroperoxide (PPHP)]- or arachidonic acid-dependent cooxidation by microsomal prostaglandin H (PGH) synthase as evidenced by UV spectroscopic analysis of reaction mixtures. Cooxidation of RA by microsomal or purified PGH synthase, using PPHP as substrate, was characterized by uptake of dioxygen which was first order with respect to enzyme concentration. Dioxygen uptake was inhibited by the peroxidase reducing substrate 2-methoxyphenol. In addition, O2 uptake was inhibited by the spin trap nitrobenzene. ESR spin trapping studies, using α-phenyl-N-tert-butylnitrone (PBN) as the spin trap, demonstrated the formation of RAP-PBN adducts, characterized by hyperfine coupling constants of aH = 3.2 G and aN = 15.8 G. Reverse phase HPLC analysis of reaction mixtures demonstrated the formation of 4-hydroxy-RA, 5,6-epoxy-RA, 4-oxo-RA, (13Z)-retinoic acid, and other geometric isomers which were identified on the basis of cochromatography with synthetic standards, UV spectroscopy, and/or mass spectrometry. Mechanisms are proposed for the hydroperoxide-dependent, PGH synthase-catalyzed oxidation of RA that are consistent with these results.
- Samokyszyn, Victor M.,Chen, Tao,Maddipati, Krishna Rao,Franz, Thomas J.,Lehman, Paul A.,Lloyd, Roger V.
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Read Online
- Preparation method of olefine acid impurity
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The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of an olefine acid impurity. The impurity is (13E) -3, 7-dimethyl -9 -[(3RS) -3-methoxy -2, 6, 6-trimethyl cyclohexenyl] -2, 4, 6, 8-azela
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Paragraph 0059-0060
(2021/01/11)
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- 4-OXO-FENRETINIDE, ADMINISTERED ALONE AND IN COMBINATION WITH FENRETINIDE, AS PREVENTIVE AND THERAPEUTIC AGENT FOR CANCER
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A drug based on a metabolite of fenretinide, or N-(4-hydroxyphenyl)retinamide (4-HPR), specifically 4-oxo-N-(4-hydroxyphenyl)retinamide (4-oxo-4-HPR), is used in the treatment of different kinds of tumors, in particular in the treatment of ovarian carcino
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Page/Page column 9-10
(2008/06/13)
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- Novel retinoic acid metabolism blocking agents endowed with multiple biological activities are efficient growth inhibitors of human breast and prostate cancer cells in vitro and a human breast tumor xenograft in nude mice
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Novel retinoic acid metabolism blocking agents (RAMBAs) have been synthesized and characterized. The synthetic features include introduction of nucleophilic ligands at C-4 of all-trans-retinoic acid (ATRA) and 13-cis-retinoic acid, and modification of ter
- Patel, Jyoti B.,Huynh, Carlic K.,Handratta, Venkatesh D.,Gediya, Lalji K.,Brodie, Angela M. H.,Goloubeva, Olga G.,Clement, Omoshile O.,Nanne, Ivo P.,Soprano, Dianne Robert,Njar, Vincent C. O.
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p. 6716 - 6729
(2007/10/03)
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- Potent inhibition of retinoic acid metabolism enzyme(s) by novel azolyl retinoids
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Novel (±)-4-azolyl retinoic acid analogues 4, 5, 7 and 8 have been designed and synthesized and have been shown to be powerful inhibitors of hamster microsomal all-trans-retinoic acid 4-hydroxylase enzyme(s). (±)-4-(1H-Imidazol-1-yl)retinoic acid (4) is t
- Njar, Vincent C.O.,Nnane, Ivo P.,Brodie, Angela M.H.
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p. 1905 - 1908
(2007/10/03)
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