Synthesis and biological evaluation of 3-arylisoquinolines as antitumor agents

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 1, 1998, Pages 41-46

  Cho, Won Jea ^a   Park, Myun Ji ^a   Chung, Byung Ho ^a   Lee, Chong Ok ^b  

^a Chonnam National University   (South Korea)

^b Screening Ctr of Korea Res I   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ARYLISOQUINOLINE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; ISOQUINOLINES; STRUCTURE-ACTIVITY RELATIONSHIP; TUMOR CELLS, CULTURED;

EID: 0032488622     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)10190-1     Document Type: Article

References (19)

1. 1. Suzuki, M., Nakanishi, T., Kogawa, O., Ishikawa, K., Kobayashi, F., Ikimoto, H., EP 487930, 1992 ; Chem. Abstr. 1992, 191706.
2. 1. Suzuki, M., Nakanishi, T., Kogawa, O., Ishikawa, K., Kobayashi, F., Ikimoto, H., EP 487930, 1992 ; Chem. Abstr. 1992, 191706.
3. 2. Kobayashi, F., Yokimoto, H., Suzuki, M., Tsubuki, M., Jpn. Kokai Tokkyo Koho JP 04364128, 1992.
4. 3. Janin, Y. L., Croisy, A., Riou, J. -F., and Bisagni, E., J. Med. Chem., 1993, 36, 3686-3692.
5. 4. Behrens, C. H., US Patent 4942163, 1990.
6. 5. Fang, S. -D., Wang, L.-K., and Hecht, S. M., J. Org. Chem., 1993, 58, 5025-5027.
7. 6. Mackay, S. P., Meth-Cohn, O., Waich, R. D., Advances in Heterocyclic Chemistry, Katritzky, A. R., Ed. ; Academic Press, 1997; Vol. 67, pp 345-389.
8. 7. Cho, W. -J., Yoo, S. -J., Chung, B.-H., Cheon, S. H., Whang, S. -H., Kim, S. -K., Kang, B.-H., Lee, C. -O., Arch. Pharm. Res., 1996, 19, 321-325.
9. 8. A first synthesis of this compound: Onda, M., and Yamaguchi, H., Chem. Pharm. Bull., 1979, 27, 2076-2083.
10. 9. Thornber, C. W., Chem. Soc. Res., 1979, 8, 563.
11. 10. Poindexter, G. S., J. Org. Chem., 1982, 47, 3787-3788.
12. 11. Cava, M. P., and Levinson, M. I., Tetrahedron, 1985, 41, 5061-5087.
13. +, 15), 313 (27), 310 (75), 297 (100).
14. 13. Rubinstein, L. V., Shoemaker, R. H., Paull, K. D., Simon, R. M., Tosini, S., Skehan, P., Scudiero, D., A., Monks, A., and Boyd, M. R., J. Natl. Cancer Inst., 1990, 82, 1113-1118.
15. 14. Skehan, P., Storeng, R., Scudiero, D., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S., and Boyd, M. R., J. Natl. Cancer Inst., 1990, 82, 1107-1112.
16. 15. Charge calculation was performed using Gasteiger method in the Sybyl program (Version 6.3) supplied by Tripos Associates, 1699 South Hanley Road, Suite 303, St. Louis, Missouri 63144, USA.
17. 16. The result of comparative molecular field analysis (CoMFA), three dimensional quantitative structure-activity relationship study, of 3-arylisoquinolines indicated that the above pharamcophore model showed quite a good correlation with the contour map derived from this computational analysis. This CoMFA result will be reported soon elsewhere.
18. 17. For testing in vivo assay of the representative compound 12a, female BDF1 mice were inoculated IP with P 388 leukemia cells (10 controls and 6 animals in each test group), and the test compound was injected intraperitoneally as 0.2 mL solutions (PBS) at 1, 3, 5, 7 and 9 days after leukemia inoculation. T/C is expressed as the ratio of the median survival time of treated animals to the median control time multiplied by 100.
19. 18. The mode of action of fagaridine (NK 109, 1) developed in Nippon Kayaku in Japan in known as topoisomerase II inhibitor. The synthesized 3-arylisoquinolines are under estimation of topoisomerase inhibition activity.