Synthesis and bioactivity of 4-alkyl(aryl)thioquinazoline derivatives

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 8, 2007, Pages 2193-2196

  Yang, Song ^a   Li, Zhi ^a   Jin, Linhong ^a   Song, Baoan ^a   Liu, Gang ^a   Chen, Jiang ^a   Chen, Zhuo ^a   Hu, Deyu ^a   Xue, Wei ^a   Xu, Ruiqing ^a  

^a BEIJING UNIVERSITY OF POSTS AND TELECOMMUNICATIONS   (China)

Author keywords

Against ERK phosphorylation; Anti cancer activity; Quinazoline; Synthesis; Thioether

Indexed keywords

ACETONE; ANTINEOPLASTIC AGENT; POTASSIUM CARBONATE; QUINAZOLINE DERIVATIVE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BIOASSAY; CANCER CELL; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL ANALYSIS; CHEMICAL MODIFICATION; CHEMICAL REACTION; CONTROLLED STUDY; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; FEMALE; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; INFRARED SPECTROSCOPY; MALE; PROTON NUCLEAR MAGNETIC RESONANCE;

ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL SURVIVAL; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FEMALE; HUMANS; INHIBITORY CONCENTRATION 50; MALE; MOLECULAR STRUCTURE; PHOSPHORYLATION; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP; SULFHYDRYL COMPOUNDS;

EID: 33947668958     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.01.101     Document Type: Article

References (15)

1. Kersemaekers A.M.F., Fleuren G.J., Kenter E.G., Van den Broek L.J.C.M., Uljee S.M., Hermans J., and Van de Vijver M.J. Clin. Cancer Res. 5 (1999) 577
2. Maurizi M., Almadori G., Ferrandina G., Distefano M., Romanini M.E., Cadoni G., Benedetti-Panici P., Paludetti G., Scambia G., and Mancuso S. Br. J. Cancer 74 (1996) 1253
3. Klohs W.D., Fry D.W., and Kraker A.J. Curr. Opin. Oncol. 9 (1997) 562
4. Voldborg B.R., Damstrup L., Spang-Thomsen M., and Poulsen H.S. Ann. Oncol. 8 (1997) 1197
5. Wang Y.D., Miller K., Boschelli D.H., Ye F., Wu B.Q., Floyd M.B., Powell D.W., Wissner A., Weber J.M., and Boschelli F. Bioorg. Med. Chem. Lett. 10 (2000) 2477
6. Wissner A., Floyd M.B., Johnson B.D., Fraser H., Ingalls C., Nittoli T., Dushin R.R., Discafani C., Nilakantan R., Marini J., Ravi M., Cheung K., Tan X., Musto S., Annable T., Siegel M.M., and Loganzo F. J. Med. Chem. 48 (2005) 7560
7. Smaill J.B., Palmer B.D., Rewcastle G.W., Denny W.A., McNamara D.J., Dobrusin E.M., Bridges A.J., Zhou H., Showalter H.D.H., Winters R.T., Leopold W.R., Fry D.W., Nelson J.M., Slintak V., Elliot W.L., Roberts B.J., Vincent P.W., and Patmore S.J. J. Med. Chem. 42 (1999) 1803
8. Woodburn J.R., Barker A.J., Gibson K.H., Ashton S.E., Wakeling A.E., Curry B.J., Scarlett L., and Henthorn L.R.Z. Proc. Am. Assoc. Cancer Res. 38 (1997) 633
9. Abdel Hamid S.G., El-Obeid H.A., Al-Rashood K.A., Khalil A.A., and El-Subbagh H.I. Sci. Pharm. 69 (2001) 351
10. Radl S., Hrzky P., Proska J., and Krejci I. Archiv. der. Pharmazie. (Weinheim, Germany) 333 (2000) 381
11. Song B.-A., Chen C.-J., Yang S., Jin L.-H., Xue W., Zhang S.-M., Zou Z.-H., Hu D.-Y., and Liu G. Acta Chimica Sinica 63 (2005) 1720
12. Jin L.H., Chen J., Song B.A., Chen Z., Yang S., Li Q.Z., Hu D.Y., and Xu R.Q. Bioorg. Med. Chem. Lett. 16 (2006) 5036
13. 3 (3.50 mmol). The mixture was then refluxed for 8 h. After cooling, the crude product was obtained by filtration and recrystallized from ethanol to afford 3a-3m as white solids. Their physicochemical properties and the spectral data can be found in supporting information.
14. 3 cells/well/100 μL of the proper culture medium and treated with the compounds at 1-100 μM for 72 h. In parallel, the cells treated with 0.1% DMSO served as control. An MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay (Roche Molecular Biochemicals, 1465-007) was performed 30 h later according to the instructions provided by Roche. This assay is based on the cellular cleavage of MTT into formazan which is soluble in cell culture medium. And the absorbance caused by formazan was measured at 595 nm with a microplate reader (Bio-Rad, model 680), which is directly proportional to the number of living cells in culture. Three types of cells were used in these assays, PC3 (prostate cancer), BGC 823 (human gastric cancer), and Bcap37 (breast cancer) cell lines, provided by ATCC and cultivated in RPMI 1640 (for PC3, BGC823, and Bcap37) supplemented with 10% fetal bovine serum. Tissue culture reagents were obtained from Gibco BRL. Skehan P., Storeng R., Scadiero D., Monks A., McMahon I., Vistica D., Warren J.T., Bokesch H., Kenney S., and Boy M.R. Natl. J. Cancer Inst. 82 (1990) 1107
15. 4, 10 mM NaF, 10 mM β-glycerophosphate, 1 mM DTT, 10 μg/mL leupeptin, 10 μg/ml pepstatin, and 40 μg/ml PMSF) and sample buffer, respectively, followed by immuno-blotting using P-ERK (E-4) (sc-7383, lot# J0803, Santa Cruz Biotechnology). Western blot analysis: The cell lysates prepared above were subjected to 10% SDS-PAGE and proteins were transferred to PVDF membranes (Bio-Rad). The membrane was blocked with 5% nonfat dried milk freshly made in PBS plus 0.2% Tween 20, then incubated with monoclonal antibody (anti-phosphotyrosine, anti-pErk1/2 or anti-caveolin) over night at 4 °C. Then the membrane was washed for 3 × 5 min with PBS plus 0.2% Tween 20. The membrane was incubated again with second antibody for 2-3 h at 25 °C, washed three times with PBS plus 0.2% Tween 20, and the signal was detected by enhanced chemical luminescence (ECL) detection system (PIERCE). Egger D., and Bienz K. Mol. Biotech. 1 (1994) 289