Synthesis and Cytotoxicity of 1,6,7,8-Substituted 2-(4′-Substituted phenyl)-4-quinolones and Related Compounds: Identification as Antimitotic Agents Interacting with Tubulin

Journal of Medicinal Chemistry

Volumn 36, Issue 9, 1993, Pages 1146-1156

  Kuo, Sheng Chu ^a   Lee, Hong Zin ^a   Juang, Jung Pin ^a   Lin, Yih Tyng ^a   Wu, Tian Shung ^b   Chang, Jer Jang ^c   Lednicer, Dan ^d   Paull, Kenneth D ^d   Lin, Chii M ^d   Hamel, Ernest ^d   Lee, Kuo Hsiung ^e  

^a China Medical College   (China)

^b NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

^c UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^d NATIONAL CANCER INSTITUTE   (United States)

^e UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 QUINOLONE DERIVATIVE; 6 CHLORO 2 PHENYL 4 QUINOLONE; 6 METHOXY 2 PHENYL 4 QUINOLONE; 7 FLUORO 2 PHENYL 4 QUINOLONE; ANTIMITOTIC AGENT; COLCHICINE; COMBRETASTATIN; PODOPHYLLOTOXIN; TUBULIN; UNCLASSIFIED DRUG;

ARTICLE; CENTRAL NERVOUS SYSTEM TUMOR; COLON CARCINOMA; CYTOTOXICITY; DRUG SYNTHESIS; INTESTINE CARCINOMA; LEUKEMIA CELL; LUNG CARCINOMA; MELANOMA; MICROTUBULE ASSEMBLY; MITOSIS INHIBITION; NASOPHARYNX CARCINOMA; NONHUMAN; PRIORITY JOURNAL;

ANIMAL; ANTINEOPLASTIC AGENTS; HUMAN; INTESTINAL NEOPLASMS; LEUKEMIA L1210; LEUKEMIA P388; LUNG NEOPLASMS; MELANOMA; MICE; MOLECULAR STRUCTURE; NASOPHARYNGEAL NEOPLASMS; QUINOLINES; QUINOLONES; SOFTWARE; STRUCTURE-ACTIVITY RELATIONSHIP; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S.; TUBULIN; TUMOR CELLS, CULTURED;

EID: 0027246046     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm00061a005     Document Type: Article

References (31)

1. Cheng, C. C. A Common Structural Pattern Among Many Biologically Active Compounds of Natural and Synthetic Origin. Med. Hypotheses 1986, 20, 157–172.
2. Huang, M. T.; Wood, A. W.; Newmark, H. L.; Sayer, J. M.; Yagi, H.; Jerina, D. M.; Conney, A. H. Inhibition of the Mutagenicity of Bay-Region Diol-Epoxides of Polycyclic Aromatic Hydrocarbons by Phenolic Plant Flavonoids. Carcinogenesis 1983, 4, 1631–1637.
3. Wattenberg, L. W.; Leong, J. L. Inhibition of the Carcinogenic Action of 7,12-Dimethylbenz[a]anthracene by Beta-Naphthofla-vone. Proc. Soc. Exptl. Biol. Med. 1968, 128, 940–943.
4. Lee, K. H.; Tagahara, K.; Suzuki, H.; Wu, R. Y.; Haruna, M.; Hall, I. H.; Huang, H. C.; Ito, K.; Iida, T.; Lai, J. S. Antitumor Agents 49: Tricin, Kaempferol-3-O-β-D-glucopyranoside and (+)-Nortrachelogenin, Antileukemic Principles from Wikstroemia indica. J. Nat. Prod. 1981, 44, 530–535.
5. Kashiwada, Y.; Nonaka, G.; Nishioka, I.; Chang, J. J.; Lee, K. H. Antitumor Agents, 129. Tannins and Related Compounds As Selective Cytotoxic Agents. J. Nat. Prod. 1992, 55, 1033–1043.
6. Goodwin, S.; Smith, A. F.; Ho, E. C. Alkaloids of Lunasia. amara Blanco. 4-Methoxy-2-phenylquinoline. J. Am. Chem. Soc. 1957, 79, 2239–2241.
7. Kasahara, A.; Izumi, T.; Watanabe, H.; Takahashi, S. A New Synthesis of 2-Aryl-4-Quinolones. Chem. Ind. (London) 1981, No. 4, 121.
8. Cheng, R. T.; Siddiqui, M. A.; Snieckus, V. Synthetic Connections to the Aromatic Directed Metalation Reaction. A Modified von Niementowski Quinoline Synthesis from Anthranilamides. Tetrahedron Lett. 1986, 27, 5323–5326.
9. Chen, B. C.; Huang, X.; Wang, J. A Versatile Synthesis of 2-Alkyl and 2-Aryl-4-Quinolones. Synthesis 1987, No. 5, 482–483.
10. Fuson, R. C.; Burness, D. M. A New Synthesis of 2-Aryl-4-Hydroxyquinolines. J. Am. Chem. Soc. 1946, 68, 1270–1272.
11. Venturella, P.; Bellino, A. On the Reactions Between Ethyl Benzoylacetate and Anisidines. J. Heterocycl. Chem. 1975, 12, 669–673.
12. Venturella, P. Q.; Bellino, A.; Marino, M. L.; Piozzi, F. Synthesis of l-Methyl-2-Phenyl-5-Hydroxy-4-Quinolone and Improved Synthesis of Edulein. Gazz. Chim. Ital. 1970, 100, 678–681.
13. Coppola, G. M. The Chemistry of 2H-3, l-Benzoxazine-2,4(1H)-dione (1satoic Anhydride) 9. Synthesis of 2-Arylquinoline Alkaloids. J. Heterocycl. Chem. 1982, 19, 727–731.
14. Singh, H.; Aggarwal, S. K.; Malhotra, N. Extrusion Reactions-VIII, A Facile Synthesis of 4-Alkyl Quinazolines and l-Methyl-2-Aryl-4-Quinolones. Tetrahedron 1986, 42, 1139–1144.
15. Staskun, B.; Israelstam, S. S. The Reaction Between β-Keto Esters and Arylamines in the Presence of Polyphosphoric Acid 1. Ethyl Benzoylacetate and Arylamines. J. Org. Chem. 1961, 26, 3191–3193.
16. Wu, T. S. Alkaloids and Coumarins of Skimma reevesiana. Phytochemistry 1987, 26, 873–875.
17. Boyd, M. R. Status of the NCI preclinical antitumor drug discovery screen. In Cancer. Principles and Practice of Oncology Updates; De Vita, V. T., Hellman, S., Rosenberg, S. A., Eds.; J. B. Lippincott: Philadelphia, 1989; pp 1–12.
18. Monks, A.; Scudiero, D.; Skehan, P.; Shoemaker, R.; Pauli, K.; Vistica, D.; Hose, C.; Langley, J.; Cronise, P.; Vaigro-Wolff, A.; Gray-Goodrich, M.; Campbell, H.; Mayo, J.; Boyd, M. Feasibility of a high-flux anticancer drug screen utilizing a diverse panel of human tumor cell lines in culture. J. Natl. Cancer Inst. 1991, 83, 757–766.
19. Pauli, K. D.; Shoemaker, R. H.; Hodes, L.; Monks, A.; Scudiero, D. A.; Rubinstein, L.; Plowman, J.; Boyd, M. R. Display and analysis of patterns of differential activity of drugs against human tumor cell lines: development of mean graph and COMPARE algorithm. J. Natl. Cancer Inst. 1989, 81, 1088–1092.
20. Bai, R.; Pauli, K. D.; Herald, C. L.; Malspeis, L.; Pettit, G. R.; Hamel, E. Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin: discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J. Biol. Chem. 1991, 266, 15882–15889.
21. Pauli, K. D.; Lin, C. M.; Malspeis, L.; Hamel, E. Identification of novel antimitotic agents acting at the tubulin level by computer-assisted evaluation of differential cytotoxicity data. Cancer Res. 1992, 52, 3892–3900. Compound B in ref 19 corresponds to compound 26 in the present manuscript, compound C to 27, and compound D to 24.
22. Hamel, E. Interactions of tubulin with small ligands. In Microtubule Proteins; Avila, J., Ed.; CRC Press: Boca Raton, FL, 1990; pp 89–91.
23. Lin, C. M.; Singh, S. B.; Chu, P. S.; Dempcy, R. O.; Schmidt, J. M.; Pettit, G. R.; Hamel, E. Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study. Mol. Pharmacol. 1988, 34, 200–208.
24. Jiang, J. B.; Hesson, D. P.; Dusak, B. A.; Dexter, D. L.; Kang, G. J.; Hamel, E. Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization. J. Med. Chem. 1990, 33, 1721–1728.
25. Lin, C. M.; Kang, G. J.; Roach, M. C.; Jiang, J. B.; Hesson, D. P.; Luduena, R. F.; Hamel, E. Investigation of the mechanism of the interaction of tubulin with derivatives of 2-styrylquinazolin-4-(3H)-3-one. Mol. Pharmacol. 1991, 40, 827–832.
26. Edwards, M. L.; Stemerick, D. M.; Sunkara, P. S. Chalcones: anew class of antimitotic agents. J. Med. Chem. 1990, 33, 1948–1954.
27. Getahun, Z.; Jurd, L.; Chu, P. S.; Lin, C. M.; Hamel, E. Synthesis of alkozy-subtituted diaryl compounds and correlation of ring separation with inhibition of tubulin polymerization: differential enhancement of inhibitory effects under suboptimal polymerization reaction conditions. J. Med. Chem. 1992, 35, 1058–1067.
28. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: Application of proliferation and cytotoxicity assay. J. Immunol. Methods 1983, 65, 55–63.
29. Hamel, E.; Lin, C. M. Separation of active tubulin and microtubule-associated proteins by ultracentrifugation and isolation of a component causing the formation of microtubule bundles. Biochemistry 1984, 23, 4173–4184.
30. Huang, A. B.; Lin, C. M.; Hamel, E. Differential effects of magnesium on tubulin-nucleotide interactions. Biochim. Biophys. Acta 1985, 832, 22–32.
31. Muzaffar, A.; Brossi, A.; Lin, C. M.; Hamel, E. Antitubulin effects of derivatives of 3-demethylthiocolchicine, methylthio ethers of natural colchicinoids, and thioketones derived from thiocolchicine. Comparison with colchicinoids. J. Med. Chem. 1990, 33, 567–571.