DP7, a novel dihydropyridine multidrug resistance reverter, shows only weak inhibitory activity on human CYP3A enzyme(s)

European Journal of Pharmacology

Volumn 614, Issue 1-3, 2009, Pages 7-13

  D'Elia, Paolo ^a   De Matteis, Francesco ^b   Dragoni, Stefania ^a   Shah, Anamik ^c   Sgaragli, Giampietro ^a   Valoti, Massimo ^a  

^a UNIVERSITY OF SIENA   (Italy)

^b MEDICAL RESEARCH COUNCIL   (United Kingdom)

^c SAURASHTRA UNIVERSITY   (India)

Author keywords

CYP isoform; DP7; Liver microsome; MDR reverter

Indexed keywords

3,5 DIBENZOYL 4 (3 PHENOXYPHENYL) 1,4 DIHYDRO 2,6 DIMETHYLPYRIDINE; CYTOCHROME P450 1A1; CYTOCHROME P450 1A2; CYTOCHROME P450 2B; CYTOCHROME P450 2C; CYTOCHROME P450 3A; CYTOCHROME P450 3A2; CYTOCHROME P450 3A4; DIHYDROPYRIDINE DERIVATIVE; DP 7; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; IC 50; LIVER MICROSOME; MALE; MULTIDRUG RESISTANCE; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RAT;

ANIMALS; CYTOCHROME P-450 CYP3A; DIHYDROPYRIDINES; DRUG RESISTANCE, MULTIPLE; HUMANS; ISOENZYMES; LIVER; MALE; MICROSOMES; P-GLYCOPROTEINS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 67349155960     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2009.04.019     Document Type: Article

References (33)

1. Abass K., Reponen P., Turpeinen M., Jalonen J., and Pelkonen O. Characterization of diuron N-demethylation by mammalian hepatic microsomes and cDNA-expressed human cytochrome P450 enzymes. Drug Metab. Dispos. 35 (2007) 1634-1641
2. Ambudkar S.V., Kimchi-Sarfaty C., Sauna Z.E., and Gottesman M.M. P-glycoprotein: from genomics to mechanism. Oncogene 22 (2003) 7468-7485
3. Bogaards J.J., Bertrand M., Jackson P., Oudshoorn M.J., Weaver R.J., van Bladeren P.J., and Walther B. Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica 30 (2000) 1131-1152
4. Chauret N., Tremblay N., Lackman R.L., Gauthier J.Y., Silva J.M., Marois J., Yergey J.A., and Nicoll-Griffith D.A. Description of a 96-well plate assay to measure cytochrome P4503A inhibition in human liver microsomes using a selective fluorescent probe. Anal. Biochem. 276 (1999) 215-226
5. Chovan J.P., Ring S.C., Yu E., and Baldino J.P. Cytochrome P450 probe substrate metabolism kinetics in Sprague Dawley rats. Xenobiotica 37 (2007) 459-473
6. De Matteis F., Hollands C., Gibbs A.H., de Sa N., and Rizzardini M. Inactivation of cytochrome P450 and production of N-alkylated porphyrins caused in isolated hepatocytes by substituted dihydropyridines. Structural requirements for loss of haem and alkylation of the pyrrole nitrogen atom. FEBS Lett. 145 (1982) 87-92
7. Donato M.T., Jiménez N., Castell J.V., and Gómez-Lechón M.J. Fluorescence-based assays for screening nine cytochrome P450 (P450) activities in intact cells expressing individual human P450 enzymes. Drug Metab. Dispos. 32 (2004) 699-706
8. Drocourt L., Pascussi J.M., Assenat E., Fabre J.M., Maurel P., and Vilarem M.J. Calcium channel modulators of the dihydropyridine family are human pregnane X receptor activators and inducers of CYP3A, CYP2B, and CYP2C in human hepatocytes. Drug Metab. Dispos. 29 (2001) 1325-1331
9. Ford J.M., and Hait W.N. Pharmacologic circumvention of multidrug resistance. Cytotechnology 12 (1993) 171-212
10. Fusi F., Saponara S., Valoti M., Dragoni S., D'Elia P., Sgaragli T., Alderighi D., Kawase M., Shah A., Motohashi N., and Sgaragli G. Cancer cell permeability-glycoprotein as a target of MDR reverters: possible role of novel dihydropyridine derivatives. Curr. Drug Targets 8 (2006) 949-959
11. Guengerich F.B., Brian W.R., Iwasaki M., Sari M.A., Baarnhielm C., and Berntsson P. Oxidation of dihydropyridine calcium channel blockers and analogues by human cytochrome P450 3A4. J. Med. Chem. 34 (1991) 1838-1844
12. Jurima-Romet M., Crawford K., Cyr T., and Inaba T. Terfenadine metabolism in human liver: in vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab. Dispos. 22 (1994) 849-857
13. Katoh M., Nakajima M., Shimada N., Yamazaki H., and Yokoi T. Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur. J. Clin. Pharmacol. 55 (2000) 843-852
14. Kawase M., Shah A., Gaveriya H., Motohashi N., Sakagami H., Varga A., and Molnár J. 3,5-dibenzoyl-1,4-dihydropyridines: synthesis and MDR reversal in tumor cells. Bioorg. Med. Chem. 10 (2002) 1051-1055
15. Lowry O.H., Rosebrough N.J., Farr A.L., and Randall R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193 (1951) 265-275
16. Ludwig E., Schmid J., Beschke K., and Ebner T. Activation of human cytochrome P-450 3A4-catalyzed meloxicam 5′-methylhydroxylation by quinidine and hydroquinidine in vitro. J. Pharmacol. Exp. Ther. 290 (1999) 1-8
17. Massey V., Komai H., Palmer G., and Elion G.B. On the mechanism of inactivation of xanthine oxidase by allopurinol and other pyrazole[3,4-d]pyrimidines. J. Biol. Chem. 245 (1970) 2837-2844
18. McCluskey S.A., Marks G.S., Sutherland E.P., Jacobsen N., and Ortiz de Montellano P.R. Ferrochelatase-inhibitory activity and N-alkylprotoporphyrin formation with analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) containing extended 4-alkyl groups: Implications for the active site of ferrochelatase. Mol. Pharmacol. 30 (1986) 352-357
19. McCluskey S.A., Riddick D.S., Mackie J.E., Kimmett R.A., Whitney R.A., and Marks G.S. Inactivation of cytochrome P450 and inhibition of ferrochelatase by analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine with 4-nonyl and 4-dodecyl substituents. Can. J. Physiol. Pharmacol. 70 (1992) 1069-1074
20. McDevitt C.A., and Callaghan R. How can we best use structural informations on P-glycoprotein to design inhibitors?. Pharmacol. Ther. 113 (2007) 429-441
21. Ninci R., and DeMatteis F. Metabolism of 7-benzyloxy-7-ethoxy- and 7-pentoxy-resorufins by liver and olfactory microsomes from rats and guinea pigs. Pharmacologyonline 3 (2005) 41-53
22. Niwa T., Shiraga T., Yamasaki S., Ishibashi K., Ohno Y., and Kagayama A. In vitro activation of 7-benzyloxyresorufin O-debenzylation and nifedipine oxidation in human liver microsomes. Xenobiotica 33 (2003) 717-729
23. Ortiz de Montellano P.R. Cytochrome P450: Structure, Mechanism and Biochemistry. Second Edition (1995), Plenum Press, New York, USA
24. Rando R.R. Mechanism-based enzyme inactivators. Pharmacol. Rev. 36 (1984) 111-142
25. Saponara S., Kawase M., Shah A., Motohashi N., Molnar J., Ugocsai K., Sgaragli G., and Fusi F. 3,5-Dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7) as a new multidrug resistance reverting agent devoid of effects on vascular smooth muscle contractility. Br. J. Pharmacol. 141 (2004) 415-422
26. Saponara S., Ferrara A., Gorelli B., Shah A., Kawase M., Motohashi N., Molnar J., Sgaragli G., and Fusi F. 3,5-dibenzoyl-4-(3-phenoxyphenyl)-1,4-dihydro-2,6-dimethylpyridine (DP7): a new multidrug resistance inhibitor devoid of effects on Langendorff-perfused rat heart. Eur. J. Pharmacol. 563 (2007) 160-163
27. Silverman R.B. Mechanism-based enzyme inactivators. Methods Enzymol. 249 (1995) 240-283
28. Stresser D.M., Blanchard A.P., Turner S.D., Erve J.C., Dandeneau A.A., Miller V.P., and Crespi C.L. Substrate-dependent modulation of CYP3A4 catalytic activity: analysis of 27 test compounds with four fluorometric substrates. Drug Metab. Dispos. 28 (2000) 1440-1448
29. Stresser D.M., Turner S.D., Blanchard A.P., Miller V.P., and Crespi C.L. Cytochrome P450 fluorometric substrates: identification of isoform-selective probes for rat CYP2D2 and human CYP3A4. Drug Metab. Dispos. 30 (2002) 845-852
30. Tipton K.F. Enzymes: irreversible inhibition. Nature Encyclopedia of Life Sciences (2001), Nature Publishing Group, London. http://www.els.net/ 10.1038/npg.els.0000601 (http://www.els.net/)
31. Wandel C., Lang C.C., Cowart D.C., Girard A.F., Bramer S., Flockhart D.A., and Wood A.J. Effect of CYP3A inhibition on vesnarinone metabolismin humans. Clin. Pharmacol. Ther. 63 (1998) 506-511
32. Zhang J.G., Dehal S.S., Ho T., Johnson J., Chandler C., Blanchard A.P., Clark Jr. R.J., Crespi C.L., Stresser D.M., and Wong J. Human cytochrome p450 induction and inhibition potential of clevidipine and its primary metabolite H152/81. Drug Metab. Dispos. 34 (2006) 734-737
33. Zhou S.F. Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr. Drug Metab. 9 (2008) 310-322