Detail of "9048-63-9"

Reference

Benzo[a]pyrene diol epoxides: mechanism of enzymic formation and optically active intermediates

Benzo[a]pyrene diol epoxides: mechanism of enzymic formation and optically active intermediates. Yang, Shen K.; McCourt, David W.; Leutz, Janet C.; Gelboin, Harry V. (Chem. Branch, Natl. Cancer Inst., Bethesda, Md., USA). Science, 196(4295), 1199-201 (English) 1977. CODEN: SCIEAS. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Studies of the mechanism of benzo[a]pyrene (I) [50-32-8] metab. to reactive diol expoxides and of their disposition indicated that the metabolic intermediates of the activation pathways, 7,8-epoxide [36504-65-1] and trans-7,8-diol, as well as the two stereoisomeric diol epoxides are all optically active. I is converted to optically active 9,10-epoxides of (-)-trans-7,8-diol by 3 enzymatic steps: (i) sterospecific oxygenation at the 7,8 double bond of I by the mixed-function oxidase [9040-60-2] to essentially a single enantiomer of 7,8-epoxide, (ii) hydration of the 7,8-epoxide by epoxide hydratase [9048-63-9] to an optically pure (-)-trans-7,8-diol [60864-95-1], and (iii) stereoselective oxygenation by the mixed-function oxidases at the 9,10 double bond of the (-)-trans-7,8-diol to optically active r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [63323-31-9] and optically active r-7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [60268-86-2] in a ratio of approx. 10 to 1.

Drug-drug interactions via inhibition of microsomal enzymes involved in metabolism of epoxides produced by microsomal monooxygenase

Drug-drug interactions via inhibition of microsomal enzymes involved in metabolism of epoxides produced by microsomal monooxygenase. Oesch, F.; Glatt, H. R.; Bentley, P. (Inst. Pharmacol., Mainz, Ger.). Microsomes Drug Oxid., Proc. Int. Symp., 3rd, Meeting Date 1976, 442-6. Edited by: Ullrich, Volker; Roots, Ivar; Hildebrandt, Alfred. Pergamon: Oxford, Engl. (English) 1977. CODEN: 36URAW. DOCUMENT TYPE: Conference CA Section: 4 (Toxicology) Benzo[a]pyrene [50-32-8] was activated by mouse liver microsomes to mutagens detected by the reversion of histidine-dependent Salmonella typhimurium TA 1537. Epoxide hydratase [9048-63-9] was found to be a crit. enzyme for the inactivation of these mutagens. The metabolically produced epoxide from the drug cyproheptadine, cyproheptadine 10,11-oxide [54191-04-7], was a potent inhibitor of rat liver microsomal styrene 7,8-oxide hydratase. In a therapeutic situation it would be expected that the concn. of the epoxides metabolically produced from the drug would be much greater than that of the epoxides produced from polycyclic hydrocarbons which are present ubiquitously, but at very low levels. Thus, competitive inhibition by the former may be very effective and may potentiate adverse biol. effects of the latter.