Development of small-molecule P-gp inhibitors of the N-benzyl 1,4-dihydropyridine type: Novel aspects in SAR and bioanalytical evaluation of multidrug resistance (MDR) reversal properties

Bioorganic and Medicinal Chemistry

Volumn 21, Issue 1, 2013, Pages 166-177

  Baumert, Christiane ^a   Günthel, Marianne ^a   Krawczyk, Sören ^a   Hemmer, Marc ^a   Wersig, Tom ^a   Langner, Andreas ^a   Molnár, Joséf ^b   Lage, Hermann ^c   Hilgeroth, Andreas ^a  

^a MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^b UNIVERSITY OF SZEGED   (Hungary)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Efflux pump inhibition; Inhibitor; Multidrug resistance (MDR); P glycoprotein (P gp); Structure activity relationships (SAR)

Indexed keywords

1 BENZYL 3 ETHOXYCARBONYLPYRIDINIUM BROMIDE; 1 BENZYL 3 METHOXYCARBONYLPYRIDINIUM BROMIDE; DAUNORUBICIN; ETHYL 1 BENZYL 1,4 DIHYDRO 4 (1 NAPHTHYL)PYRIDINE 3 CARBOXYLATE; ETHYL 1 BENZYL 4 (2 METHOXYPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; ETHYL 1 BENZYL 4 (3 BROMOPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; ETHYL 1 BENZYL 4 (3 CHLOROPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; ETHYL 1 BENZYL 4 (3 TRIFLUOROPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; ETHYL 1 BENZYL 4 (4 METHOXYPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; ETHYL 1 BENZYL 4 (4 TOLYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; ETHYL 1,4 DIHYDRO 1 (1 NAPHTHYLMETHYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; ETHYL 1,4 DIHYDRO 1 (2 METHOXYBENZYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; ETHYL 1,4 DIHYDRO 1 (4 METHOXYBENZYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; ETHYL 1,4 DIHYDRO 1 (4 METHYLBENZYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; GLYCOPROTEIN P INHIBITOR; METHYL 1 BENZYL 4 (2 METHOXYPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; METHYL 1 BENZYL 4 (3 BROMOPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; METHYL 1 BENZYL 4 (3 CHLOROPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; METHYL 1 BENZYL 4 (3 TRIFLUOROPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; METHYL 1 BENZYL 4 (4 METHOXYPHENYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; METHYL 1 BENZYL 4 (4 TOLYL) 1,4 DIHYDROPYRIDINE 3 CARBOXYLATE; METHYL 1,4 DIHYDRO 1 (1 NAPHTHYLMETHYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; METHYL 1,4 DIHYDRO 1 (2 METHOXYBENZYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; METHYL 1,4 DIHYDRO 1 (4 METHOXYBENZYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; METHYL 1,4 DIHYDRO 1 (4 METHYLBENZYL) 4 PHENYLPYRIDINE 3 CARBOXYLATE; MULTIDRUG RESISTANCE PROTEIN; N BENZYL 1,4 DIHYDROPYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ANALYTIC METHOD; ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL VIABILITY; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG STRUCTURE; DRUG SYNTHESIS; IC 50; LYMPHOMA CELL LINE; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; CELL LINE, TUMOR; CELL SURVIVAL; DAUNORUBICIN; DIHYDROPYRIDINES; DRUG RESISTANCE, MULTIPLE; DRUG RESISTANCE, NEOPLASM; HUMANS; MICE; NEOPLASMS; P-GLYCOPROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84870928241     PISSN: 09680896     EISSN: 14643391     Source Type: Journal    
DOI: 10.1016/j.bmc.2012.10.041     Document Type: Article

References (27)

1. M.M. Gottesman, and V. Ling FEBS Lett. 580 2006 998
2. H. Lage Cell. Mol. Life Sci. 65 2008 3145
3. P.D.W. Eckford, and F.J. Sharom Chem. Rev. 109 2009 2989
4. C. Baumert, and A. Hilgeroth Anti-Cancer Agents Med. Chem. 9 2009 415
5. F.X. Mahon, F. Belloc, V. Lagarde, C. Chollet, F. Moreau-Gaudry, J. Reiffers, J.M. Goldman, and J.V. Melo Blood 101 2003 2368
6. H. Matsui, A. Takeshita, K. Naito, K. Shinjo, K. Shigeno, M. Maekawa, Y. Yamakaw, M. Tanimito, M. Kobayashi, K. Ohnishi, and R. Ohno Leukemia 16 2002 813
7. F.J. Sharom Pharmacogenomics 9 2008 105
8. C.-H. Choi Cancer Cell Int. 5 2005 30
9. C. Avendanó, and J.C. Menéndez Med. Chem. Rev. 1 2004 419
10. A. Krühn, A. Wang, J.H. Fruehauf, and H. Lage Cell Cycle 20 2009 3349
11. R. Krishna, and L.D. Mayer Eur. J. Pharm. Sci. 11 2000 265
12. A. Seelig, and E. Landwojtowicz Eur. J. Pharm. Sci. 12 2000 31
13. R.J. Kelly, D. Draper, and C.C. Chen Clin. Cancer Res. 17 2011 569
14. M. Kawase, and N. Motohashi Curr. Drug Targets 4 2003 31
15. H. Lage, N. Duarte, C. Coburger, A. Hilgeroth, and M.J.U. Ferreira Phytomedicine 17 2010 441
16. S. Krawczyk, M. Otto, A. Otto, C. Coburger, M. Krug, M. Seifert, V. Tell, J. Molnár, and A. Hilgeroth Bioorg. Med. Chem. 19 2011 6309
17. A. Hilgeroth, K. Brachwitz, and U. Baumeister Heterocycles 55 2001 661
18. G. Battistuzzi, S. Cacchi, and G. Fabrizi Org. Lett. 5 2003 777
19. J.G. McVie F.M. Muggia, Cancer Treatment and the Hart 1992 Johns Hopkins University Press Baltimore 92
20. Y.E. Rahman, W.R. Hanson, J. Bharucha, E.J. Ainsworth, and B.N. Jaroslow Ann. N.Y. Acad. Sci. 308 1987 325
21. P. Guaglianone, K. Chan, E. DelaFlor-Weiss, R. Hanisch, and S. Jeffers Invest. New Drugs 12 1994 103
22. A.F. Mohrbacher, S.A. Gregory, D.A. Gabriel, J.M. Rusk, and F.J. Giles Cancer 94 2002 2645
23. T. Koike, M. Tanabe, N. Takeuchi, and S. Tobinga Chem. Pharm. Bull. 45 1997 1117
24. R. Fossheim, A. Joslyn, A.J. Solo, E. Luchowski, A. Rutledge, and D.J. Triggle J. Med. Chem. 31 1988 300
25. J.J. Baldwin, D.A. Clareman, P.K. Lumma, D.E. McClure, S.A. Rosenthal, R.J. Winquist, E.R. Fairson, G.J. Kaczorowski, M.J. Trumble, and G.M. Smith J. Med. Chem. 30 1987 690
26. J.L. Weaver, D. Szabo, P.S. Pine, S. Gottesmann, A. Goldberg, and A. Aszalos Int. J. Cancer 54 1993 456
27. M.M. Cornwell, I. Pastan, and M.M. Gottesmann J. Biol. Chem. 262 1987 2166