Synthesis and cytotoxic evaluation of certain 4-anilino-2-phenylquinoline derivatives.
The present report describes the synthesis and cell growth inhibition of certain 4-anilino-2-phenylquinoline derivatives. 4-(4-Acetylphenylamino)-6-methoxy-2-phenylquinoline (11), its oxime 15a, and its methyloxime 15b, exhibited significant cytotoxicity against all 60 cancer cells with mean GI(50) values of 3.89, 3.02, and 3.89 microM, respectively, while 4-(4-acetylanilino)-6-methoxy-2-phenylquinoline-3-carboxylic acid (9) and its 3-carboxylic acid congeners 13a, 13b, 14a, and 14b were inactive, indicated free carboxylic acid at C(3) position is unfavorable. The steric hindrance exerted by the 3-carboxylate in 9, 13, and 14 may prevent the adjacent phenyl ring to lie coplanar with quinoline, which leads to the devoid of cytotoxicity. The comparable cytotoxicity of oxime 15a, methyloxime 15b, and the ketone precursor 11 implied a hydrogen-bonding accepting group at C(4) position of 4-anilino-moiety is crucial for cytotoxicity. Among these compounds, 11 is especially active against the growth of certain solid cancer cells such as NCI-H226 (non-small cell lung cancer), MDA-MB-231/ATCC (breast cancer), and SF-295 (CNS cancer) with GI(50) values of 0.94, 0.04, and<0.01 microM respectively.
Zhao
Yue-Ling
YL
Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City, Taiwan, ROC.
Chen
Yeh-Long
YL
Chang
Feng-Shuo
FS
Tzeng
Cherng-Chyi
CC
D000814:Aniline Compounds / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019800:Phenol / Q000737:chemistry* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000814:Aniline Compounds; D000970:Antineoplastic Agents; D011804:Quinolines; D019800:Phenol; C023650:aniline