Metabolism of 3-cyanomethyl-4-methyl-DCK, a new anti-HIV candidate, in human intestinal microsomes

Yaoxue Xuebao

Volumn 45, Issue 9, 2010, Pages 1116-1122

  Zhuang, Xiao Mei ^a   Wen, Yuan Yuan ^a   Li, Hua ^a   Deng, Jing Ting ^a   Kong, Wei Li ^a   Tian, Xing Tao ^a   Cui, Shu Li ^a   Xie, Lan ^a  

^a BEIJING INSTITUTE OF MICROBIOLOGY AND EPIDEMIOLOGY   (China)

Author keywords

Anti HIV candidate; CMDCK; Intestinal metabolism; Microsome; Recombinant CYP enzyme

Indexed keywords

3 CYANOMETHYL 4 METHYL 3',4' DI O CAMPHANOYLKHELLACTONE DERIVATIVE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 INHIBITOR; KETOCONAZOLE; RITONAVIR; TROLEANDOMYCIN; UNCLASSIFIED DRUG;

ARTICLE; DRUG BIOAVAILABILITY; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME KINETICS; HUMAN; HUMAN TISSUE; INTESTINE; INTESTINE BLOOD FLOW; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MICROSOME; OXIDATION;

ANTI-HIV AGENTS; BICYCLO COMPOUNDS, HETEROCYCLIC; BIOLOGICAL AVAILABILITY; COUMARINS; CYTOCHROME P-450 CYP3A; HUMANS; INTESTINES; KETOCONAZOLE; METABOLIC CLEARANCE RATE; MICROSOMES; RITONAVIR; TROLEANDOMYCIN;

EID: 78349235887     PISSN: 05134870     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (14)

1. van Herwaarden AE, van Waterschoot RA, Schinkel AH. How important is intestinal cytochrome P450 3A metabolism? [J]. Trends Pharmacol Sci, 2009, 30: 223-227.
2. Liu Z, Ma YM, Wang TM, et al. In vitro metabolic interconversion between baicalin and baicale in the liver, kidney, intestine and bladder of rat [J]. Acta Pharm Sin, 2008, 43: 664-668.
3. Xie L, Yu D, Wild C, et al. Anti-AIDS agents 52. Synthesis and anti-HIV activity of hydroxymethyl (3′R, 4′R)-3′, 4′-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK) derivatives [J]. J Med Chem, 2004, 47: 756-760. (Pubitemid 38129733)
4. Xie LC, Zhao H, Zhuo T, et al. Molecular modeling, design, synthesis, and biological evoluation of novel 3′, 4′-di-O-(S)-camphanoyl-(+)-cis- khellactone (DCK) analogues as potent anti-HIV agents [J]. Bioorg Med Chem, 2005, 13: 6435-6449.
5. Huang L, Yuan X, Yu DL, et al. Mechanism of action and resistant profile of anti-HIV coumarin derivatives [J]. Virology, 2005, 332: 623-628.
6. Xie L, Guo HF, Lu H, et al. Development and preclinical studies of broad-spectrum anti-HIV agent (3′R, 4′R)-3-cyanomethyl-4-methyl- 3′, 4′-di-O-(S)-camphanoyl-(+)- cis-khellactone (3-cyanomethyl-4- methyl-DCK) [J]. J Med Chem, 2008, 51: 7689-7696.
7. Motohiro KATO. Intestinal first-pass metabolism of CYP3A4 substrates [J]. Drug Metab Pharmacokinet, 2008, 23: 87-94.
8. Suzuki M, Li Y, Smith PC, et al. Anti-AIDS agents 65: investigation of the in vitro oxidative metabolism of 3′, 4′-di-O-(-)-camphanoyl-(+)- cis-khellactone derivatives as potent anti-AIDS agents [J]. Drug Metab Dispos, 2005, 33: 1588-1592.
9. Zhang QY, Kaminsky LS, Dunbar D, et al. Role of small intestinal cytochromes P450 in the bioavailability of oral nifedipine [J]. Drug Metab Dispos, 2007, 35: 1617-1623.
10. Galetin A, Gertz M, Houston JB. Potential role of intestinal first-pass metabolism in the prediction of drug-drug interactions [J]. Exp Opin Drug Metab Toxicol, 2008, 4: 909-921.
11. Hisaka A, Ohno Y, Yamamoto T, et al. Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information [J]. Pharmacol Ther, 2010, 125: 230-248.
12. Eagling VA, Back DJ, Barry MG, et al. Differential inhibition of cytochrome P450 isoforms by the protease inhibitors: ritonavir, saquinavir and indinavir [J]. Bri J Clin Pharmacol, 1997, 44: 190-194.
13. Ripamonti D, Maggiolo F. Rilpivirine, a non-nucleoside reverse transcriptase inhibitor for the treatment of HIV infection [J]. Curr Opin Invest Drugs, 2008, 9: 899-912.
14. Grime KH, Bird J, Ferguson D, et al. Mechanism-based inhibition of cytochrome P450 enzymes: an evaluation of early decision making in vitro approaches and drug-drug interaction prediction methods [J]. Eur J Pharm Sci, 2009, 36: 175-191.