4′-Alkoxyl substitution enhancing the anti-mitotic effect of 5-(3′,4′,5′-substituted)anilino-4-hydroxy-8-nitroquinazolines as a novel class of anti-microtubule agents

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 22, 2006, Pages 5864-5869

  Jin, Yi ^a   Zhou, Zu Yu ^a   Tian, Wei ^b   Yu, Qiang ^a   Long, Ya Qiu ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Alkoxyl substitution; Aniline; Anti microtubule agent; Antiproliferative effect; Cell cycle; Mitosis inhibitor; Quinazoline; Tubulin polymerization; Tumor cells

Indexed keywords

5 (30,40,50 TRIMETHOXY)ANILINO 8 NITROQUINAZOLINE; ANILINE DERIVATIVE; QUINAZOLINE DERIVATIVE; UNCLASSIFIED DRUG; ALCOHOL DERIVATIVE; ALKOXY RADICAL; ANTIMITOTIC AGENT;

ARTICLE; CANCER INHIBITION; CELL CYCLE ARREST; CELL CYCLE G2 PHASE; CELL CYCLE M PHASE; CONTROLLED STUDY; DRUG ACTIVATION; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; MICROTUBULE; MITOSIS; SUBSTITUTION REACTION; CELL DIVISION; CHEMISTRY; DRUG EFFECT; PHYSIOLOGY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE;

ALCOHOLS; ANILINE COMPOUNDS; ANTIMITOTIC AGENTS; CELL DIVISION; CELL LINE, TUMOR; G2 PHASE; HUMANS; MICROTUBULES; MITOSIS; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 33749264426     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.08.058     Document Type: Article

References (22)

1. Connolly D.J., Cusack D., O'Sullivan T.P., and Guiry P.J. Tetrahedron 61 (2005) 10153
2. Ciardiello F., and Tortora G. Clin. Cancer Res. 7 (2001) 2958
3. Ballard P., Bradbury R.H., Hennequin L.F.A., Hickinson D.M., Johnson P.D., Kettle J.G., Klinowska T., Morgentin R., Ogilvie D.J., and Olivier A. Bioorg. Med. Chem. Lett. 15 (2005) 4226
4. Bathini Y., Singh I., Harvey P.J., Keller P.R., Singh R., Micetich R.G., Fry D.W., Dobrusin E.M., and Toogood P.L. Bioorg. Med. Chem. Lett. 15 (2005) 3881
5. Gungor T., Chen Y., Golla R., Ma Z.P., Corte J.R., Northrop J.P., Bin B., Dickson J.K., Stouch T., Zhou R., Johnson S.E., Seethala R., and Feyen J.H.M. J. Med. Chem. 49 (2006) 2440
6. Jin Y., Li H.-Y., Lin L.-P., Tan J., Luo X., Ding J., and Long Y.-Q. Bioorg. Med. Chem. 13 (2005) 5613
7. Qin, L.; Ai, M.; Tian, W.; Jin, Y.; Zhou, Z.-Y.; He, J.; Long, Y.-Q.; Yu, Q. A novel synthetic analog of 5,8-disubstituted quinazoline blocks mitosis and induces apoptosis of tumor cells by inhibiting microtubule polymerization. Unpublished results.
8. Margolis R.L., and Wilson L. Bioessays 20 (1998) 830
9. Jordan M.A., and Wilson L. Nat. Rev. Cancer 4 (2004) 253
10. Mani S., Macapinlac Jr. M., Goel S., Verdier-Pinard D., Fojo T., Rothenberg M., and Colevas D. Anti cancer Drugs 15 (2004) 553
11. Rowinsky E.K., and Tolcher A.W. Antimicrotubule agents. In: Devita Jr. V.T., Hellman S., and Rosenberg S.A. (Eds). Cancer Principles and Practice. 6th ed. (2001), Lippincott Williams and Willkins, Philadelphia 431
12. Gottesman M.M. Annu. Rev. Med. 53 (2002) 615
13. Dumontet C., and Sikic B.I. J. Clin. Oncol. 17 (1999) 1061
14. 6). C, H, N: 54.84, 4.33, 15.05. Found: 54.76, 4.42, 15.14.
15. Muathen H.A. Molecules 8 (2003) 593
16. Cell Growth Inhibition Assay. Two human carcinoma cell lines, A549 (lung adenocarcinoma) and HGC-27 (gastrointestinal carcinoma), were used for the cell proliferation assay. A549 cells were cultured in RPMI-1640 medium supplemented with 10% calf serum; HGC-27 cells were cultured in DMEM supplemented with 10% calf serum. The growth inhibition was examined by MTT assay.
17. Mossman T. J. Immunol. Methods 65 (1983) 55
18. Cell mitosis assay by flow cytometry analysis. Tumor cells were incubated with indicated concentration of synthetic inhibitor for 24 h. The harvested cells were washed with PBS, resuspended in 1 mL of iced 75% ethanol at -20 °C. After being left to stand overnight, cell pellets were collected by centrifugation, resuspended in 500 μL of hypotonic buffer (0.5% Triton X-100 in PBS and 0.5 μg/mL RNase), and incubated at 37 °C for 30 min. Then 25 μL of propidium iodide solution (50 μg /mL) was added, and the mixture was allowed to stand on ice for 1 h. Fluorescence emitted from the propidium iodide-DNA complex was quantitated after excitation of the fluorescent dye by FAC-Scan cytometry. The histogram of DNA distribution was modeled as a sum of G1, G2-M, S phase, and an aneuploid population close to the G1 peak, by using ModFitLT software.
19. Yoshida D., Hoshino S., Shimura T., Tahakashi H., and Teramoto A. J. Neurooncol. 47 (2000) 133
20. Ravelli R.B., Gigant B., Curmi P.A., Jourdain I., Lachkar S., Sobel A., and Knossow M. Nature 428 (2004) 198
21. Morris G.M., Goodsell D.S., Halliday R.S., Huey R., Hart W.E., Belew R.K., and Olson A.J. J. Comput. Chem. 19 (1998) 1639
22. Morris, G. M.; Goodsell, D. S.; Huey, R.; Hart, W. E.; Halliday, R. S.; Belew, R. K.; Olson, A. J. AUTODOCK, M. Version 3.0.3. The Scripps Research Institute, Molecular Graphics Laboratory, Department of Molecular Biology, 1999.