Novel lead for potent inhibitors of breast cancer resistance protein (BCRP)

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 1, 2010, Pages 180-183

  Pick, Anne ^a   Müller, Henrik ^a   Wiese, Michael ^a  

^a UNIVERSITY OF BONN   (Germany)

Author keywords

ABCG2; BCRP; Hoechst 33342; Inhibitors; Multidrug resistance; Pheophorbide A

Indexed keywords

1,2,3,4,6,7,12,12A OCTAHYDRO 6 ISOBUTYL 9 METHOXY 1,4 DIOXOPYRAZINO[1',2':1,6]PYRIDO[3,4 B]INDOLE 3 PROPANOIC ACID TERT BUTYL ESTER; ANTINEOPLASTIC AGENT; BREAST CANCER RESISTANCE PROTEIN; ELACRIDAR; GEFITINIB; IMATINIB; NOVOBIOCIN; PROTEIN INHIBITOR; TARIQUIDAR;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG INHIBITION; DRUG STRUCTURE; HUMAN; HUMAN CELL; HYDROGEN BOND;

ATP-BINDING CASSETTE TRANSPORTERS; BENZAMIDES; BENZIMIDAZOLES; CELL LINE, TUMOR; CHLOROPHYLL; HUMANS; MOLECULAR CONFORMATION; NEOPLASM PROTEINS; PHENYLUREA COMPOUNDS; SMALL MOLECULE LIBRARIES;

EID: 72049094261     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.11.004     Document Type: Article

References (27)

1. Bodo A., Bakos E., Szeri F., Varadi A., and Sarkadi B. Toxicol. Lett. 140-141 (2003) 133
2. Doyle L.A., Yang W., Abruzzo L.V., Krogmann T., Gao Y., Rishi A.K., and Ross D.D. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 15665
3. Henriksen U., Gether U., and Litman T. J. Cell Sci. 118 (2005) 1417
4. Borst P., Evers R., Kool M., and Wijnholds J. J. Natl. Cancer Inst. 92 (2000) 1295
5. Doyle L.A., and Ross D.D. Oncogene 22 (2003) 7340
6. Suzuki M., Suzuki H., Sugimoto Y., and Sugiyama Y. J. Biol. Chem. 278 (2003) 22644
7. Robey R.W., Medina-Perez W.Y., Nishiyama K., Lahusen T., Miyake K., Litman T., Senderowicz A.M., Ross D.D., and Bates S.E. Clin. Cancer Res. 7 (2001) 145
8. Ahmed-Belkacem A., Pozza A., Macalou S., Perez-Victoria J.M., Boumendjel A., and Di Pietro A. Anticancer Drugs 17 (2006) 239
9. Rabindran S.K., Ross D.D., Doyle L.A., Yang W., and Greenberger L.M. Cancer Res. 60 (2000) 47
10. Allen J.D., van Loevezijn A., Lakhai J.M., van der Valk M., van Tellingen O., Reid G., Schellens J.H., Koomen G.J., and Schinkel A.H. Mol. Cancer Ther. 1 (2002) 417
11. Shiozawa K., Oka M., Soda H., Yoshikawa M., Ikegami Y., Tsurutani J., Nakatomi K., Nakamura Y., Doi S., Kitazaki T., Mizuta Y., Murase K., Yoshida H., Ross D.D., and Kohno S. Int. J. Cancer 108 (2004) 146
12. Clark R., Kerr I.D., and Callaghan R. Br. J. Pharmacol. 149 (2006) 506
13. Ahmed-Belkacem A., Pozza A., Munoz-Martinez F., Bates S.E., Castanys S., Gamarro F., Di Pietro A., and Perez-Victoria J.M. Cancer Res. 65 (2005) 4852
14. Yanase K., Tsukahara S., Asada S., Ishikawa E., Imai Y., and Sugimoto Y. Mol. Cancer Ther. 3 (2004) 1119
15. Kühnle M., Egger M., Müller C., Mahringer A., Bernhardt G., Fricker G., König B., and Buschauer A. J. Med. Chem. 52 (2009) 1190
16. Roe M., Folkes A., Ashworth P., Brumwell J., Chima L., Hunjan S., Pretswell I., Dangerfield W., Ryder H., and Charlton P. Bioorg. Med. Chem. Lett. 9 (1999) 595
17. Klinkhammer W., Müller H., Globisch C., Pajeva I.K., and Wiese M. Bioorg. Med. Chem. 176 (2009) 2524
18. Müller H., Klinkhammer W., Globisch C., Kassack M.U., Pajeva I.K., and Wiese M. Bioorg. Med. Chem. 15 (2007) 7470
19. Pick A., Müller H., and Wiese M. Bioorg. Med. Chem. 16 (2008) 8224
20. 2. When achieving a confluence of 80-90% cells were treated with trypsin-EDTA before subculturing. Every 5th passage mitoxantrone (0.1 μM final concentration) was added to the cell culture medium to maintain ABCG2 overexpression. Before performing an experiment, mitoxantrone was removed from the cell suspension and cells were cultivated at least one passage in the absence of the cytostatic drug.
21. max-values were defined as responses. From these data, concentration-response curves were generated by nonlinear regression using the 4-parameter logistic equation with variable Hill slope (graphpad prism 5.0 software, San Diego, CA).
22. Merino G., Jonker J.W., Wagenaar E., van Herwaarden A.E., and Schinkel A.H. Mol. Pharmacol. 67 (2005) 1758
23. 3 channel (633 nm). Cell debris or dead cells were eliminated by gating on forward versus side scatter. The measured fluorescence was defined as response to generate concentration-response curves corresponding to the procedure described above.
24. We confirmed the overexpression of BCRP in MCF-7 MX and MDCK BCRP cells applying the BCRP specific antibody 5D3 which recognizes an external epitope of BCRP. Following the manufactures preparation procedure equal quantities of MCF-7 MX, MCF-7, MDCK and MDCK BCRP cells were analyzed by flow cytometry detection. The results, presented as geometric means of fluorescence, prove that BCRP is highly overexpressed in MCF-7 MX (215 ± 3) and MDCK BCRP cells (215 ± 3). The labeling of MCF-7 (9.7 ± 0.4) and MDCK cells (9.8 ± 0.3) was negligible illustrating that BCRP is not present in these cells.
25. The cells were prepared as described above and seeded into colorless 96-well plates (Greiner, Frickenhausen, Germany) at a density of approximately 30,000 cells per well (one well including 90 μl cell suspension and 10 μl test compound solution). After the preincubation period with the test compounds, 33 μl of a 1.25 μM calcein AM solution which was protected from light was added to each well. The fluorescence was detected immediately at constant time intervals (120 s) up to 46 min at an excitation wavelength of 485 nm and an emission wavelength of 520 nm applying a 37 °C tempered BMG POLARstar microplate reader. The fluorescence-data points were measured up to 46 min and the slopes were calculated by linear regression and used as dependent parameters. From these data concentration-response curves were generated by nonlinear regression using the 4-parameter logistic equation with variable Hill slope (graphpad prism 5.0 software, San Diego, CA).
26. Müller H., Pajeva I.K., Globisch C., and Wiese M. Bioorg. Med. Chem. 16 (2008) 2456
27. As no X-ray data of the compounds were available, the energy minimized conformers were generated using stochastic search. In the stochastic search the MMFF94s force field was applied with the default sybyl settings. To ensure a better sampling of conformational space the following parameters were defined: energy cut off 10 kcal/mol, failure limit 200 (continuous number of attempts to generate a new conformation), RMS tolerance 0.5, iteration limit 20,000, and minimization iteration limit 2000.