N-Aryltriazole ribonucleosides with potent antiproliferative activity against drug-resistant pancreatic cancer

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 8, 2010, Pages 2503-2507

  Liu, Yang ^a   Xia, Yi ^b   Fan, Yuting ^a   Maggiani, Alain ^b   Rocchi, Palma ^c   Qu, Fanqi ^a   Iovanna, Juan L ^c   Peng, Ling ^b  

^a WUHAN UNIVERSITY   (China)

^b AIX MARSEILLE UNIVERSITÉ   (France)

^c INSERM   (France)

Author keywords

N Arylated triazole nucleoside; N Arylation; Nucleosides; Pancreatic cancer; Triazole nucleosides

Indexed keywords

BORONIC ACID DERIVATIVE; GEMCITABINE; PACLITAXEL; RIBONUCLEOSIDE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CONTROLLED STUDY; CROSS COUPLING REACTION; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; PANCREAS CANCER; STRUCTURE ACTIVITY RELATION;

CELL LINE, TUMOR; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; PANCREATIC NEOPLASMS; RIBONUCLEOSIDES;

EID: 77950042736     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.02.104     Document Type: Article

References (36)

1. Claire S. Nucleoside Mimetics: Their chemistry and biological properties; Advanced Chemistry Texts (2001), Gordon and Beach Science, UK
2. In: Herdewijn P. (Ed). Modified Nucleosides in Biochemistry, Biotechnology and Medicine (2008), Wiley-VCH, Weinheim
3. Xia Y., Liu Y., Wan J.Q., Wang M.H., Rocchi P., Qu F.Q., Iovanna J.L., and Peng L. J. Med. Chem. 52 (2009) 6083
4. Wan J.Q., Xia Y., Liu Y., Wang M.H., Rocchi P., Yao J.H., Qu F.Q., Neyts J., Iovanna J.L., and Peng L. J. Med. Chem. 52 (2009) 1144
5. Zhu R.Z., Wang M.H., Xia Y., Qu F.Q., Neyts J., and Peng L. Bioorg. Med. Chem. Lett. 18 (2008) 3321
6. Xia Y., Li W., Qu F.Q., Fan Z.J., Liu X.F., Berro C., Rauzy E., and Peng L. Org. Biomol. Chem. 5 (2007) 1695
7. Xia Y., Fan Z.J., Yao J.H., Liao Q., Li W., Qu F.Q., and Peng L. Bioorg. Med. Chem. Lett. 16 (2006) 2693
8. Xia Y., Qu F.Q., Li W., Wu Q.Y., and Peng L. Heterocycles 65 (2005) 345
9. Li W., Xia Y., Fan Z.J., Qu F.Q., Wu Q.Y., and Peng L. Tetrahedron Lett. 49 (2008) 2804
10. Zhu R.Z., Qu F.Q., Quéléver G., and Peng L. Tetrahedron Lett. 48 (2007) 2389
11. Wan J.Q., Zhu R.Z., Xia Y., Qu F.Q., Wu Q.Y., Yang G.F., Neyts J., and Peng L. Tetrahedron Lett. 47 (2006) 6727
12. Li W., Fan Y.T., Xia Y., Rocchi P., Zhu R.Z., Qu F.Q., Neyts J., Iovanna J., and Peng L. Helv. Chim. Acta 92 (2009) 1503
13. Li D., Xie K., Wolff R., and Abbruzzese J.L. Lancet 363 (2004) 1049
14. Rivera F., López-Tarruella S., Vega-Villegas M.E., and Salcedo M. Cancer Treat. Rev. 35 (2009) 335
15. Pierantoni C., Pagliacci A., Scartozzi M., Berardi R., Bianconi M., and Cascinu S. Crit. Rev. Oncol. Hematol. 67 (2008) 27
16. Mini E., Nobili S., Caciagli B., Landini I., and Mazzei T. Ann. Oncol. 17 Suppl 5 (2006) v7
17. Wong H.H., and Lemoine N.R. Nat. Rev. Gastroenterol. Hepatol. 6 (2009) 412
18. Loakes D. Nucleic Acids Res. 29 (2001) 2437
19. Xia, Y.; Wan, J. Q.; Qu, F. Q.; Peng, L. Synthesis of Nucleoside Analogues with Aromatic Systems Appended on the Triazole Nucleosides. In Chemistry of Nucleic Acid Components, Hocek, M.; Eds.; Collection Symposium Series; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic: Prague 2008; Vol. 10, pp 224-228.
20. Arrigo A.-P., Simon S., Gibert B., Kretz-Remy C., Nivon M., Czekalla A., Guillet D., Moulin M., Diaz-Latoud C., and Vicart P. FEBS Lett. 581 (2007) 3665
21. Concannon C.G., Gorman A.M., and Samali A. Apoptosis 8 (2003) 61
22. Mori-Iwamoto S., Kuramitsu Y., Ryozawa S., Mikuria K., Fujimoto M., Maehara S.-I., Maehara Y., Okita K., Nakamura K., and Sakaida I. Int. Journal Oncol. 31 (2007) 1345
23. Mori-Iwamoto S., Taba K., Kuramitsu Y., Ryozawa S., Tanaka T., Maehara S.-I., Maehara Y., Okita K., Nakamura K., and Sakaida I. Pancreas 38 (2009) 224
24. Rocchi P., So A., Kojima S., Signaevsky M., Beraldi E., Fazli L., Hurtado-coll A., Yamanaka K., and Gleave M. Cancer Res. 64 (2004) 6595
25. Rocchi P., Beraldi E., Ettinger S., Fazli L., Vessella R.L., Nelson C., and Gleave M. Cancer Res. 65 (2005) 11083
26. Evano G., Blanchard N., and Toumi M. Chem. Rev. 108 (2008) 3054
27. Wu Q.Y., Qu F.Q., Wan J.Q., Zhu X., Xia Y., and Peng L. Helv. Chim. Acta 87 (2004) 811
28. Wu Q.Y., Qu F.Q., Wan J.Q., Xia Y., and Peng L. Nucleosides, Nucleotides Nucleic Acids (2005) 999
29. 2 at a pressure of 1 atm. After the complete consumption of the starting material (detected with TLC), the mixture was filtered over Celite, the filtrate was concentrated under reduced pressure, giving 0.92 g of 1 as white powder in the yield of 98%.
30. General procedure for preparing 2 via copper-mediated N-arylation with arylboronic acid: To a mixture of 3-amino-1-[2,3,5-tri-O-acetyl-β-d-ribofuranosyl]-1,2,4-triazole-5-carboxylate (100.0 mg, 0.25 mmol), 6 equiv arylboronic acid (1.50 mmol) and 68.2 mg anhydrous copper acetate (0.38 mmol) was added 5 mL dichloromethane (distilled freshly over calcium hydride). Then, 40.2 μL freshly distilled pyridine (0.50 mmol) and ca. 20 mg powder of 4 Å molecular sieve (activated at 500 °C for 5 h) were added rapidly. The mixture was stirred at room temperature for 3 days, and then filtered over Celite. The filtration was concentrated under reduced pressure, and the obtained residue was purified on silica gel with petroleum ether/ethyl acetate (1:1, v/v), giving the corresponding product 2 as powder.
31. 2. The washed residue was dried in vacuo to afford the corresponding product 3.
32. 2 for 48 h. The number of viable cells remaining after the appropriate treatment with 50 μM compound was determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT) colorimetric assay.
33. Compound 4 was synthesized following the protocol described in Ref. 9.
34. Compound 6 was synthesized following the protocol described in Ref. 8.
35. 6 cells/dish and allowed to adhere and proliferate overnight. Culture medium was then removed and fresh media containing the 50 μM concentration of compound was added. No treatment was done as negative controls. After 48 h of treatment, the cells were trypsinized and the collected cell pellet was washed with PBS and fixed in cold-ethanol 70% overnight at 4 °C. After a wash with phosphate-citrate buffer, cells were treated with 200 μL RNase (500 μg/mL), labeled with 1 mL propidium iodide (50 μg/mL), and immediately analyzed by fluorescence-activated cell sorting (FACS Calibur, Becton Dickinson, Le Pont-De-Claix, France). Each sample was performed in triplicate.
36. Caspase-3/7 cleavage assay: Caspase-3/7 activity was measured using the Caspase-Glo 3/7 Assay Kit (Promega). MiaPaCa-2 cells were initially seeded at 15,000 cells/well on 96-well plates. Twenty-four hours later, cells were treated with the test compound at 50 μM for 24 h. Next 100 μL of Caspase-Glo 3/7 Assay Reagent was added to each well of a white 96-well plate containing 100 μL of blank, control or cells in culture. The caspase-3/7 activity was measured by the cleavage of the luminogenic substrate containing the tetrapeptide sequence DEVD according to the instructions of the manufacturer (Promega). The plate was incubated at room temperature for 1 h before measuring the luminescence of each well. Each experiment was performed in triplicate.