Synthesis and Antitumor Activity of Fused Quinoline Derivatives

• Published in: Chemical & pharmaceutical bulletin Vol. 38; no. 11; pp. 3048 - 3052
• Main Authors: YANATO, Masatoshi, TAKEUCHI, Yasuo, CHANG, Ming-rong, HASHIGAKI, Kuniko, TSURUO, Takashi, TASHIRO, Tazuko, TSUKAGOSHI, Shigeru
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1990; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; antitumor activity; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Humans; indoloquinoline; intercalation; KB Cells; Mice; Models, Molecular; molecular graphics; Organic chemistry; Preparations and properties; Quinolines - chemical synthesis; Quinolines - pharmacology; synthesis; topoisomerase II; Antineoplastic agent; Sulfonamide; Ether; Structure activity relation; Nitrogen heterocycle; Benzenic compound; Aromatic compound; Tetracyclic compound; Biological activity; Secondary amine
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.38.3048

Some tetracyclic quinolines (9 and 14) with a [2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino side chain were prepared and their deoxyribonucleic acid (DNA) intercalative properties, KB cytotoxicity, antitumor activity (P388 leukemia), and ability to induce topoisomerase II dependent DNA cleavage were investigated. The indoloquinoline derivative 9 exhibited the most potent activity (dose=6.3mg, T/C%=300) in this series. The steric structural features of the chromophores of the compounds previously and newly synthesized were studied by a computer-associated molecular graphics technique. Relationships between the steric structural features of the chromophores and biological activities are also discussed.