Synthesis and biological evaluation of new phenothiazine derivatives bearing a pyrazole unit as protein farnesyltransferase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 22, Issue 22, 2012, Pages 6896-6902

  Baciu Atudosie, Lavinia ^a   Ghinet, Alina ^a,b,c   Farce, Amaury ^b,d   Dubois, Joëlle ^e   Belei, Dalila ^a   Bîcu, Elena ^a  

^a ALEXANDRU IOAN CUZA UNIVERSITY OF IASI   (Romania)

^b UNIV LILLE   (France)

^c Ecole des Hautes Etudes d'Ingenieur   (France)

^d Faculté des Sciences Pharmaceutiques et Biologiques Université de Lille   (France)

^e INSTITUT DE CHIMIE DES SUBSTANCES NATURELLES   (France)

Author keywords

Acylhydrazone; Cytostatic agent; Farnesyltransferase inhibitor; Phenothiazine; Pyrazole; Pyrazoline

Indexed keywords

CYTOSTATIC AGENT; PHENOTHIAZINE DERIVATIVE; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PYRAZOLE DERIVATIVE;

ANTIPROLIFERATIVE ACTIVITY; ARTICLE; CANCER CELL CULTURE; CELL GROWTH; CELL LINE; CELL STRAIN HCT116; CYTOSTASIS; DRUG ACTIVITY; DRUG DESIGN; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; MOLECULAR DOCKING;

ALKYL AND ARYL TRANSFERASES; BINDING SITES; CATALYTIC DOMAIN; CELL LINE, TUMOR; CELL SURVIVAL; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; HUMANS; MOLECULAR DOCKING SIMULATION; PHENOTHIAZINES; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84867863001     PISSN: 0960894X     EISSN: 14643405     Source Type: Journal    
DOI: 10.1016/j.bmcl.2012.09.030     Document Type: Article

References (43)

1. J. Ohkanda, D.B. Knowles, M.A. Blaskovich, S.M. Sebti, and A.D. Hamilton Curr. Top. Med. Chem. 2 2002 303
2. P. Haluska, G.K. Dy, and A.A. Adjei Eur. J. Cancer 38 2002 1685
3. Zhang H. Handb Metalloproteins 3 2004 37
4. H.W. Park, and L. Beese Curr. Opin. Struct. Biol. 7 1997 873
5. K. Asoh, M. Kohchi, I. Hyoudoh, T. Ohtsuka, M. Masubuchi, K. Kawasaki, H. Ebiike, Y. Shiratori, T.A. Fukami, O. Kondoh, T. Tsukaguchi, N. Ishii, Y. Aoki, N. Shimma, and M. Sakaitani Bioorg. Med. Chem. Lett. 19 2009 1753 and references cited therein
6. P. Russo, M. Loprevite, A. Cesario, and A. Ardizzoni Curr. Med. Chem. Anticancer Agents 4 2004 123
7. I.M. Bell J. Med. Chem. 2004 1869 47
8. S.B. Singh, and R.B. Lingham Curr. Opin. Drug Discov. Devel. 5 2002 225
9. D. Belei, C. Dumea, A. Samson, A. Farce, J. Dubois, E. Bîcu, and A. Ghinet Bioorg. Med. Chem. Lett. 22 2012 4517
10. A. Ghinet, B. Rigo, J. Dubois, A. Farce, J.-P. Hénichart, and P. Gautret Med. Chem. Commun. 3 2012 1147
11. D. Zhang, G. Wang, G. Zhao, W. Xu, and L. Huo Eur. J. Med. Chem. 46 2011 5868
12. B. Insuasty, A. Tigreros, F. Orozco, J. Quiroga, R. Abonía, M. Nogueras, A. Sanchez, and J. Cobo Bioorg. Med. Chem. 18 2010 4965
13. A.M. Farag, A.S. Mayhoub, S.E. Barakat, and A.H. Bayomi Bioorg. Med. Chem. 16 2008 881
14. M.A. El-borai, H.F. Rizk, M.F. Abd-Aal, and I.Y. El-Deeb Eur. J. Med. Chem. 48 2012 92
15. S.M. Riyadh, T.A. Farghaly, M.A. Abdallah, M.M. Abdalla, and M.R. Abd El-Aziz Eur. J. Med. Chem. 45 2010 1042
16. X. Li, J.-L. Liu, X.-H. Yang, X. Lu, T.-T. Zhao, H.-B. Gong, and H.-L. Zhu Bioorg. Med. Chem. 20 2012 4430
17. M.C. Franchini, B.F. Bonini, C.M. Camaggi, D. Gentili, A. Pession, M. Rani, and E. Strocchi Eur. J. Med. Chem. 45 2010 2024
18. A. Balbi, M. Anzaldi, C. Macciò, C. Aiello, M. Mazzei, R. Gangemi, P. Castagnola, M. Miele, C. Rosano, and M. Viale Eur. J. Med. Chem. 46 2011 5293
19. S. Yamamoto, N. Tomita, Y. Suzuki, T. Suzaki, T. Kaku, T. Hara, M. Yamaoka, N. Kanzaki, A. Hasuoka, A. Baba, and M. Ito Bioorg. Med. Chem. 20 2012 2338
20. W.-K. Choi, M.I. El-Gamal, H.S. Choi, D. Baek, and C.-H. Oh Eur. J. Med. Chem. 46 2011 5754
21. Y. Zhao, G. Wang, W. Dong, Y. Shi, B. Li, S. Wang, and Z. Li ARKIVOC ii 2010 16
22. P. Longhin Bosquesi, T.R. Ferreira Melo, E. Oliveira Vizioli, J.L. dos Santos, and M.C. Chung Pharmaceuticals 4 2011 1450
23. K. Pluta, B. Morak-Młodawska, and M. Jeleń Eur. J. Med. Chem. 46 2011 3179
24. T.N. Bansode, R.M. Ansari, and Y.K. Gawale J. Pharm. Res. 4 2011 1141
25. R. Santucci, P.A. Mackley, S. Sebti, and M. Alsina Cancer Control 10 2003 384
26. S. Rao, D. Cunningham, A. de Gramont, W. Scheithauer, M. Smakal, Y. Humblet, G. Kourteva, T. Iveson, T. Andre, J. Dostalova, A. Illes, R. Belly, J.J. Perez-Ruixo, Y.C. Park, and P.A. Palmer J. Clin. Oncol. 22 2004 3950
27. Q. Li, T. Li, K.W. Woods, W.-Z. Gu, J. Cohen, V.S. Stoll, T. Galicia, C. Hutchins, D. Frost, S.H. Rosenberg, and H.L. Sham Bioorg. Med. Chem. Lett. 15 2005 2918
28. F.R. Khuri, B.S. Glisson, E.S. Kim, P. Statkevich, P.F. Thall, M.L. Meyers, R.S. Herbst, R.F. Munden, C. Tendler, Y. Zhu, S. Bangert, E. Thompson, C. Lu, X.M. Wang, D.M. Shin, M.S. Kies, V. Papadimitrakopoulou, F.V. Fossella, P. Kirschmeier, W.R. Bishop, and W.K. Hong Clin. Cancer Res. 10 2004 2968
29. J.T. Hunt, C.Z. Ding, R. Batorsky, M. Bednarz, R. Bhide, Y. Cho, S. Chong, S. Chao, J. Gullo-Brown, P. Guo, S.H. Kim, F.Y. Lee, K. Leftheris, A. Miller, T. Mitt, M. Patel, B.A. Penhallow, C. Ricca, W.C. Rose, R. Schmidt, W.A. Slusarchyk, G. Vite, and V. Manne J. Med. Chem. 43 2000 3587
30. Baciu-Atudosie, L.; Ghinet, A.; Belei, D.; Gautret, P.; Rigo, B.; Bîcu, E. Tetrahedron Lett. Accepted manuscript, doi: http://dx.doi.org/10. 1016/j.tetlet.2012.08.152.
31. E.F. Godefroi, and E.L. Wittle J. Org. Chem. 21 1956 1163
32. M.B. Hogale, and D.S. Deshmukh J. Indian Chem. Soc. 66 1989 212 213
33. S.D. Srivastava, and P. Kohli Proc. Natl. Acad. Sci.; India, Sect. B 77 2007 199
34. G.F. de Sousa, E. Garcia, C.C. Gatto, I.S. Resck, and V.M. Deflon J. Mol. Struct. 981 2010 46
35. Y. Zhao, A. Bacher, B. Illarionov, M. Fischer, G. Georg, Q.-Z. Ye, P.E. Fanwick, S.G. Franzblau, B. Wan, and M. Cushman J. Org. Chem. 74 2009 5297
36. K.C. Joshi, R. Bohra, and B.S. Joshi Inorg. Chem. 31 1992 598
37. S. Gupta, L.M. Rodrigues, A.P. Esteves, A.M.F. Oliveira-Campos, M.S.J. Nascimento, N. Nazareth, H. Cidade, M.P. Neves, E. Fernandes, M. Pinto, N.M.F.S.A. Cerqueira, and N. Brás Eur. J. Med. Chem. 43 2008 771
38. A.M.F. Oliveira-Campos, A.M. Salaheldin, and L.M. Rodrigues ARKIVOC xvi 2007 92
39. 2 and 0.2% (w/v) octyl-ß-d-glucopyranoside, 52 mM Tris/HCl, pH 7.5). Fluorescence was recorded for 15 min (0.7 s per well, 20 repeats) at 30 °C with an excitation filter at 340 nm and an emission filter of 486 nm. Each measurement was reproduced in duplicate. The kinetic experiments were realized under the same conditions, either with FPP as varied substrate with a constant concentration of Dns-GCVLS of 2.5 μM, or with Dns-GCVLS as varied substrate with a constant concentration of FPP of 10 μM. Non linear regressions were performed with KaleidaGraph 4.03 software. Coudray, L.; de Figueiredo, R. M.; Duez, S.; Cortial, S.; Dubois, J. J. Enz. Inh. Med. Chem. 2009, 24, 972.
40. Cell proliferation assay: Six compounds were tested against a panel of 60 human cancer cell lines at the National Cancer Institute, Bethesda, MD. The cytotoxicity studies were conducted using a 48 h exposure protocol using the sulforhodamine B assay R.B. Boyd The NCI in vitro anticancer drug discovery screen B. Teicher, Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval 1997 Humana Press Inc. Totowa NJ 23
41. P. Skehan, R. Storeng, D. Scudiero, A. Monks, J. McMahon, D. Vistica, J.T. Warren, H. Bokesh, S. Kenney, and M.R. Boyd J. Natl. Cancer Inst. 82 1990 1107
42. Molecular modelling: Based on previous studies, 1LD7 (Bell, I. M.; Gallicchio, S. N.; Abrams, M.; Beese, L. S.; Beshore, D. C.; Bhimnathwala, H.; Bogusky, M. J.; Buser, C. A.; Culberson, J. C.; Davide, J.; Ellis-Hutchings, M.; Fernandes, C.; Gibbs, J. B.; Graham, S. L.; Hamilton, K. A.; Hartman, G. D.; Heimbrook, D. C.; Homnick, C. F.; Huber, H. E.; Huff, J. R.; Kassahun, K.; Koblan, K. S.; Kohl, N. E.; Lobell, R. B.; Lynch Jr.; J. J.; Robinson, R.; Rodrigues, A. D.; Taylor, J. S.; Walsh, E. S.; Williams, T. M.; Zartman, C. B. J. Med. Chem. 2002, 45, 2388) was chosen due to the structural similarity of the cocrystallized ((20S)-19,20,22,23-tetrahydro-19-oxo-5H,21H-18,20-ethano-12,14- etheno-6,10-methenobenz[d]imidazo[4,3-l][1,6,9,13]oxatriazacyclonoadecosine-9- carbonitrile) ligand with the compounds related in this work. The reference ligand and water molecules were removed, then the cocrystallized inhibitor was repositioned into the binding site defined as a 10 Å sphere around its position in the crystal, needing a distance constraint to maintain proximity to the zinc. This constraint was later withdrawn as metal atoms were directly taken into account by newer versions docking software and the studied compounds became more remote from the cocrystallized inhibitor. The protonation state of the protein and ligands was found to be compatible with a pH of 7.5 and the geometry of the ligands optimized using Gasteiger-Hückel partial charges, with a formal charge of +2 applied to iron atoms and a dielectric constant set to 4. After applying a formal charge of +2 on the farnesyltransferase zinc, metal atoms were handled by GOLD with the default geometry corresponding to their coordination. The 30 docking solutions were ranked based on a consensus scoring by GoldScore and X Score, then, visually inspected to assess the consistency of the best ranking conformation and select the most inhibitory clusters or conformation, when several were found.
43. Millet, R.; Domarkas, J.; Houssin, R.; Gilleron, P.; Goossens, J.-F.; Chavatte, P.; Logé, C.; Pommery, N.; Pommery, J.; Hénichart, J.-P. J. Med. Chem. 2004, 47, 6812.