Pinoline may be used as a probe for CYP2D6 activity was written by Jiang, Xi-Ling;Shen, Hong-Wu;Yu, Ai-Ming. And the article was included in Drug Metabolism and Disposition in 2009.Category: indole-building-block This article mentions the following:
Pinoline, 6-methoxy-1,2,3,4-tetrahydro-尾-carboline, is a serotonin analog that selectively inhibits the activity of monoamine oxidase-A and shows antidepressant activity. Our previous study using a panel of recombinant cytochrome P 450 (P 450) enzymes suggests that pinoline O-demethylation may be selectively catalyzed by polymorphic CYP2D6. The current study, therefore, aimed to delineate the impact of CYP2D6 status on pinoline metabolism Enzyme kinetic studies using recombinant CYP2D6 allelic isoenzymes revealed that CYP2D6.2 exhibited 5-fold lower enzyme efficiency (Vmax/Km) toward pinoline compared with CYP2D6.1, and CYP2D6.10 did not show any catalytic activity. Inhibition study showed that quinidine (1 渭M) completely blocked pinoline O-demethylase activity in human liver microsomes, whereas other P 450 isoform-selective inhibitors had no or minimal effects. Pinoline O-demethylase activities in 10 human liver microsomes showed significantly strong correlation with bufuralol 1′-hydroxylase activities (R2 = 0.93; p < 0.0001) and CYP2D6 contents (R2 = 0.82; p = 0.005), whereas no appreciable correlations with enzymic activities of other P 450 enzymes were found. Furthermore, we compared pinoline urinary metabolic ratio (pinoline/6-hydroxy-1,2,3,4-tetrahydro-尾-carboline) between CYP2D6-humanized and wild-type control mice after i.p. injection of pinoline (30 mg/kg). Results indicated that the two genotyped mice were clearly distinguished by pinoline metabolic ratio (mean 卤 S.D.), which was much higher in wild-type mice (0.29 卤 0.19, n = 4) than in CYP2D6-humanized transgenic mice (0.0070 卤 0.0048, n = 4). Our findings suggest that pinoline O-demethylation is governed by CYP2D6 status, and pinoline, at a proper concentration or dose, may be a good probe to evaluate CYP2D6 activity. In the experiment, the researchers used many compounds, for example, 6-Methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (cas: 20315-68-8Category: indole-building-block).
6-Methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (cas: 20315-68-8) belongs to indole derivatives. Indole exists overwhelmingly in the 1H-indole form as do other simple indoles. More than 200 indole derivatives have already been marketed as drugs or are under advanced stages of clinical trials.Category: indole-building-block
Referemce:
Indole alkaloid derivatives as building blocks of natural products from聽Bacillus thuringiensis聽and聽Bacillus velezensis聽and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles