Synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives.
The present report describes the synthesis and antiproliferative evaluation of certain 4-anilino-8-methoxy-2-phenylquinoline and 4-anilino-8-hydroxy-2-phenylquinoline derivatives. The antiproliferative activity of 4'-COMe-substituted derivatives decreased in an order of 6-OMe (1, 3.89 microM) > 8-OMe (8, 10.47 microM) > 8-OH (9, 14.45 microM), indicating that the position of substitution at the quinoline ring is crucial. For 3'-COMe derivatives, the antiproliferative activity of 8-OH (11, 1.20 microM) is more potent than its 8-OMe counterpart (10, 8.91 microM), indicating that a H-bonding donating substituent is more favorable than that of a H-bonding accepting group. Comparison of 8-OH derivatives, the antiproliferative effect of COMe (11) is more potent than its oxime derivative (15a, 2.88 microM), which in turn is more potent than the methyloxime counterpart (15b, 5.50 microM). Compound 11 is especially active against the growth of certain solid cancer cells such as HCT-116 (colon cancer), MCF7, and MDA-MB-435 (breast cancer) with GI50 values of 0.07, <0.01, and <0.01 microM, respectively. Flow cytometric analyses revealed that growth inhibition by 11 and 15a was due to accumulation in S-phase. This result is interesting because 2-phenylquinolone derivatives have been reported to be antimitotic agents which induced cell cycle arrest in G2/M phase.
Chen
Yeh-Long
YL
Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
Huang
Chao-Jhieh
CJ
Huang
Zun-Yuan
ZY
Tseng
Chih-Hua
CH
Chang
Feng-Shuo
FS
Yang
Sheng-Huei
SH
Lin
Shinne-Ren
SR
Tzeng
Cherng-Chyi
CC
D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C511117:4-anilino-8-hydroxy-2-phenylquinoline; C511116:4-anilino-8-methoxy-2-phenylquinoline; D000814:Aniline Compounds; D050256:Antimitotic Agents; D011804:Quinolines