High impact information on NSC210759

• This study established that ActD binds to DNA through intercalation of the phenoxazone chromophore between (G-C).(G-C) steps with the benzenoid and quinonoid-linked cyclic pentapeptide lactone rings spanning two base-pairs in opposite directions in the minor groove of the helix [1].
• Cytochrome P-450-dependent biotransformation of a series of phenoxazone ethers in the rat conceptus during early organogenesis: evidence for multiple P-450 isoenzymes [2].
• A series of phenoxazone ethers utilized as substrate probes revealed that human embryonic hepatic, pulmonary, renal, adrenal and cardiac tissues each contained a complement of functional P450 isoforms when analyzed between days 50 and 60 of gestation [3].
• The structure-activity relationship and inhibitor data for the phenoxazone substrates are consistent with a view that mouse lung and sking cyt [4].
• Liver, lung and skin microsomes each showed very different structure-activity relationships, however, for metabolism of the phenoxazone series of substrates [4].

Biological context of NSC210759

• Further investigations strongly suggested that virtually all dealkylation or debenzylation of phenoxazone ethers catalyzed by embryonic cytosolic fractions could be accounted for by the presence of Hgb in those fractions [5].
• Stereoselective and regioselective hydroxylation of warfarin and selective O-dealkylation of phenoxazone ethers in human placenta [6].

Anatomical context of NSC210759

• The oxidative metabolism of warfarin and a series of phenoxazone ethers was studied in two groups of human placentas which exhibited high or low levels of aryl hydrocarbon hydroxylase (AHH) [6].

Associations of NSC210759 with other chemical compounds

• Investigations of catalysis of the O-dealkylation and O-debenzylation of phenoxazone (resorufin) ethers in human and rodent embryonic tissue homogenates indicated that, with few exceptions, each conceptal tissue investigated contained enzymes capable of catalyzing each of the reactions under study [5].
• The high AHH group metabolized the methyl, ethyl, propyl and butyl ethers of phenoxazone rapidly, while the low AHH group catalyzed their biotransformation at very low or negligible rates [6].
• Differential effects of phenobarbitone and 3-methylcholanthrene induction on the hepatic microsomal metabolism and cytochrome P-450-binding of phenoxazone and a homologous series of its n-alkyl ethers (alkoxyresorufins) [7].
• 1. The specific activities of hepatic microsomal cortisol 6beta-hydroxylase, coumarin 7-hydroxylase, S-mephenytoin 4'-hydroxylase and phenoxazone hydroxylase and the O-dealkylations of seven homologous alkoxyresorufins were < 3-fold different between the untreated (UT) cynomolgus monkey and man [8].
• Substitution with electron-withdrawing groups such as NO2 (at C-7) and chloro (at C-1, C-2 and C-4)3 facilitated the reduction of the phenoxazone ring system to a free radical (i.e., half-wave potentials; 1, -0.815 V; 2, -0.920 V; 3, -0.135 V) [9].

Gene context of NSC210759

• The metabolism and cytochrome P-450-binding of phenoxazone and a homologous series of its n-alkyl ethers (1-8C) was studied in hepatic microsomes of control, phenobarbitone-pretreated (PB) and 3-methylcholanthrene-pretreated (3MC) C57/BL10 mice [7].
• ESR experiments confirm that the first reduction wave corresponds to a one-electron transfer process which produces a phenoxazone free radical anion and the second wave corresponds to a subsequent one-electron transfer producing a diamagnetic dianion [9].

References