Decomposition of the Telomere-Targeting agent BRACO19 in physiological media results in products with decreased inhibitory potential

International Journal of Pharmaceutics

Volumn 357, Issue 1-2, 2008, Pages 6-14

  Taetz, S ^a   Murdter T E ^b   Zapp, J ^a   Boettcher, S ^a   Baldes, C ^a   Kleideiter, E ^b   Piotrowska, K ^b   Schaefer, U F ^a   Klotz, U ^b   Lehr, C M ^a  

^a SAARLAND UNIVERSITY   (Germany)

^b UNIVERSITY OF TÜBINGEN   (Germany)

Author keywords

Acridine; Deamination; G quadruplex; Hydrolysis; Stability; TRAP assay

Indexed keywords

ACRIDINE; AMINOACRIDINE DERIVATIVE; BRACO19; TELOMERASE;

ARTICLE; DEAMINATION; DRUG STABILITY; DRUG STRUCTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PH; PRIORITY JOURNAL; TELOMERE; TELOMERIC REPEAT AMPLIFICATION PROTOCOL; TEMPERATURE;

ACRIDINES; BUFFERS; CELLS, CULTURED; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DRUG STABILITY; GENE AMPLIFICATION; HALF-LIFE; HYDROGEN-ION CONCENTRATION; HYDROLYSIS; MAGNETIC RESONANCE SPECTROSCOPY; MASS SPECTROMETRY; SOLUBILITY; SOLVENTS; SPECTROPHOTOMETRY, ULTRAVIOLET; TELOMERE; TEMPERATURE;

EID: 42749095866     PISSN: 03785173     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ijpharm.2008.01.026     Document Type: Article

References (19)

1. Blackburn E.H. Telomeres and telomerase: their mechanisms of action and the effects of altering their functions. FEBS Lett. 579 (2005) 859
2. Burger A.M., Dai F., Schultes C.M., Reszka A.P., Moore M.J., Double J.A., and Neidle S. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. Cancer Res. 65 (2005) 1489-1496
3. Cuesta J., Read M.A., and Neidle S. The design of G-quadruplex ligands as telomerase inhibitors. Mini Rev. Med. Chem. 3 (2003) 11-21
4. De Cian A., Cristofari G., Reichenbach P., De Lemos E., Monchaud D., Teulade-Fichou M.P., Shin-Ya K., Lacroix L., Lingner J., and Mergny J.L. Reevaluation of telomerase inhibition by quadruplex ligands and their mechanisms of action. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 17347-17352
5. Goodell J., Svensson B., and Ferguson D. Spectrophotometric determination and computational evaluation of the rates of hydrolysis of 9-amino-substituted acridines. J. Chem. Inf. Model. 46 (2006) 876-883
6. Gowan S.M., Harrison J.R., Patterson L., Valenti M., Read M.A., Neidle S., and Kelland L.R. A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity. Mol. Pharmacol. 61 (2002) 1154-1162
7. Harrison R.J., Cuesta J., Chessari G., Read M.A., Basra S.K., Reszka A.P., Morrell J., Gowan S.M., Incles C.M., Tanious F.A., Wilson W.D., Kelland L.R., and Neidle S. Trisubstituted acridine derivatives as potent and selective telomerase inhibitors. J. Med. Chem. 46 (2003) 4463-4476
8. Harrison R.J., Reszka A.P., Haider S.M., Romagnoli B., Morrell J., Read M.A., Gowan S.M., Incles C.M., Kelland L.R., and Neidle S. Evaluation of by disubstituted acridone derivatives as telomerase inhibitors: the importance of G-quadruplex binding. Bioorg. Med. Chem. Lett. 14 (2004) 5845-5849
9. Kim N.W., Piatyszek M.A., Prowse K.R., Harley C.B., West M.D., Ho P.L., Coviello G.M., Wright W.E., Weinrich S.L., and Shay J.W. Specific association of human telomerase activity with immortal cells and cancer. Science 266 (1994) 2011-2015
10. Kim N.W., and Wu F. Advances in quantification and characterization of telomerase activity by the telomeric repeat amplification protocol (TRAP). Nucleic Acids Res. 25 (1997) 2595-2597
11. Martins C., Gunaratnam M., Stuart J., Makwana V., Greciano O., Reszka A.P., Kelland L.R., and Neidle S. Structure-based design of benzylamino-acridine compounds as G-quadruplex DNA telomere targeting agents. Bioorg. Med. Chem. Lett. 17 (2007) 2293-2298
12. Moore M.J., Schultes C.M., Cuesta J., Cuenca F., Gunaratnam M., Tanious F.A., Wilson W.D., and Neidle S. Trisubstituted acridines as G-quadruplex telomere targeting agents. Effects of extensions of the 3,6- and 9-side chains on quadruplex binding, telomerase activity, and cell proliferation. J. Med. Chem. 49 (2006) 582-599
13. Pendino F., Tarkanyi I., Dudognon C., Hillion J., Lanotte M., Aradi J., and Ségal-Bendirdjian E. Telomeres and telomerase: pharmacological targets for new anticancer strategies?. Curr. Cancer Drug Targets 6 (2006) 147-180
14. Piotrowska K., Kleideiter E., Mürdter T.E., Taetz S., Baldes C., Schaefer U., Lehr C.M., and Klotz U. Optimization of the TRAP assay to evaluate specificity of telomerase inhibitors. Lab. Invest. 85 (2005) 1565-1569
15. Read M.A., Wood A.A., Harrison J.R., Gowan S.M., Kelland L.R., Dosanjh H.S., and Neidle S. Molecular modeling studies on G-quadruplex complexes of telomerase inhibitors: structure-activity relationships. J. Med. Chem. 42 (1999) 4538-4546
16. Riou J.F. G-quadruplex interacting agents targeting the telomeric G- overhang are more than simple telomerase inhibitors. Curr. Med. Chem. Anticancer Agents 4 (2004) 439-443
17. Shay J.W., and Wright W.E. Senescence and immortalization: role of telomeres and telomerase. Carcinogenesis 26 (2004) 867-874
18. Shay J.W., and Wright W.E. Telomerase therapeutics for cancer: challenges and new directions. Nat. Rev. Drug Discov. 5 (2006) 577-584
19. Taetz S., Baldes C., Mürdter T.E., Kleideiter E., Piotrowska K., Bock U., Haltner-Ukomadu E., Mueller J., Huwer H., Schaefer U.F., Klotz U., and Lehr C.M. Biopharmaceutical characterization of the telomerase inhibitor BRACO19. Pharm. Res. 23 (2006) 1031-1037