Synthesis and antiproliferative evaluation of 6-arylindeno[1,2-c]quinoline derivatives.
A number of 6-arylindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities against the growth of five cancer cell lines including human hepatocelluar carcinoma (Hep G2, Hep 3B and Hep2.2.1), non-small cell lung cancer (A549 and H1299), and normal diploid embryonic lung cell line (MRC-5). The preliminary results indicated that 9-(3-(dimethylamino)propoxy)-6-(4-(3-(dimethylamino)propoxy)phenyl)-2-fluoro-11H-indeno[1,2-c]quinolin-11-one (14c) was the most potent with GI(50) values of 0.61, 0.67, 0.59, and 0.72 microM against the growth of Hep G2, Hep 3B, Hep 2.2.1, and H1299 cells, respectively. Results have also shown that 2,9-bis(3-(dimethylamino)propoxy)-6-(4-(3-(dimethylamino)propoxy)phenyl)-11H-indeno[1,2-c]quinolin-11-one (17), which exhibited GI(50) of 0.60 and 0.68 microM against the growth of Hep G2 and A549, respectively, was more active than the positive topotecan and irinotecan. Compound 17 was less toxic than topotecan against the growth of normal cell (MRC-5) and therefore, was selected for further evaluation. Results indicated that compound 17 induce cell cycle arrest in G2/M phase, DNA fragmentation, and disrupt the microtubule network in A549 cells. The apoptotic induction may through the cleavage of PARP.
Tseng
Chih-Hua
CH
Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
Chen
Yeh-Long
YL
Chung
Kuin-Yu
KY
Cheng
Chih-Mei
CM
Wang
Chi-Huei
CH
Tzeng
Cherng-Chyi
CC
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase; D006801:Humans; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
D000970:Antineoplastic Agents; D007192:Indenes; D011804:Quinolines; D014404:Tubulin; D011065:Poly(ADP-ribose) Polymerases