取代的Indoloquinoline類化合物之合成與生物活性研究

Studies on the Synthesis and Biological Activities of Substituted Indoloquinolines

洪憲明(Hsien-Ming Hung)

指導教授 ： 曾誠齊 ； 陳義龍

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2003年)

摘要

角形之indolo[3,2-c]quinoline類、及線形之indolo[2,3-b]quinoline類共平面多融合雜環芳香化合物，為已知具有抗癌活性之DNA崁入劑，而在環上特定位置之取代基團可影響抗癌活性的強弱及選擇性。本文將探討6位置有脂肪族胺取代基團之indolo[3,2-c]quinoline類、及11位置有苯胺類或甲氧取代基團之indolo[2,3-b]quinoline類衍生化合物之合成途徑，並評估其生物活性。

關鍵字

角形indoloquinoline ； 線形indoloquinoline ； DNA崁入劑

並列摘要

Fused nitrogen containing heteroaromatic tetracyclo compounds, such as angular indolo[3,2-c]quinolines and linear indolo[2,3-b]quinolines are known as DNA intercalating agent with anticancer activity. Certain substituted indoloquinolines, 6-diamine substituted indolo[3,2-c]quinolines, 11-anilinoindolo[2,3-b]quinolines, and 11-methoxyindolo[2,3-b]quinolines have been synthesized and evaluated in vitro against a 3-cell line panel consisting of MCF7 (Breast), NCI-H460 (Lung), and SF-268 (CNS).

並列關鍵字

Indolo[3 ； 2-c]quinoline ； Indolo[2 ； 3-b]quinoline ； DNA intercalating agent

參考文獻

1. Wall, M. E.; Wani, M. C.; Cook, C. E.; Palmer, K. H. “ The Isolation and Structure of Camptothecin, a Novel Alkaloidal Leukemia and Tumor Inhibitor from Camptotheca acuminata ’’ J. Am. Chem. Soc., 1966, 88, 3888.

2. Hsiang, T. H.; Hertzberg, R.; Hecht, S.; Liu, L. F. “ Camptothecin Induces Protein-Linked DNA Breaks via Mammalian DNA Topoisomerase I ” J. Biol. Chem., 1985, 260, 14873.

3. Hertzbery, R. P.; Caranfa, M. J.; Holden, K. G.; Jakas, D. R.; Gallagher, G.; Mattern, M. R.; Mong, S. M.; O’Leary, J.; Jahnson, R. K.; Kingsbury, W. D. “ Modification of the Hydroxy Lactone Ring of Camptothecin: Inhibition of Mammalian Topoisomerase I and Biological Activity ” J. Med. Chem., 1989, 32. 715.

4. Kingsbury, W. D.; Boehm, J. C.; Jakas, D. R.; Holden, K. G.; Hecht, S. M.; Gallagher, G.; Caranfa, M. J.; McCabe, F. L.; Faucette, L. F.; Johnson, R. K.; Hertzbery, R. P. “ Synthesis of Water-Soluble (Aminoalkyl)camptothecin Analogues: Inhibition of Topoisomerase I and Antitumor Activity ” J. Med. Chem., 1991, 34, 98.

5. Cheng, C. C.; Liu, D. F.; Chou, T. C. “ Design of antineoplastic agents on the basis of the ‘2-phenylnaphthalene-type’ structure pattern. I. Synthesis of substituted 3-phenylquinazolones, benzoxazolo[2,3-b]quinazolones and benzothiazolo[2,3-b]quinazolones.” Heterocycles, 1993, 35, 775.