title: Synthesis and cytotoxic activity evaluation of indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones and 6-anilinoindoloquinoline derivatives.
abstract: Certain indolo-, pyrrolo-, and benzofuro-quinolin-2(1H)-ones 4a,b, 6, 8, 16a-c and 6-anilinoindoloquinoline derivatives 10a,b, 11a,b, 12a,b have been synthesized and evaluated in vitro against a 3-cell lines panel consisting of MCF7 (Breast), NCI-H460 (Lung), and SF-268 (CNS). Those active compounds 4a,b, 6, 8, 10a,b, 11a,b, 12a,b were then evaluated in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results have shown that cytotoxicity decreases in the order of 6-anilinoindoloquinolines>indoloquinolin-2(1H)-ones>pyrroloquinolin-2(1H)-ones>benzofuroquinolin-2(1H)-ones. Among them, 1-[3-(11H-indolo[3,2-c]quinolin-6ylamino)phenyl]ethanone oxime hydrochloride (11a) and its 2-chloro derivative (11b) were most active, with mean GI(50) values of 1.70 and 1.35 microM, respectively. Both compounds 11a,b were also found to inhibit the growth of SNB-75 (CNS cancer cell) with a GI(50) value of less than 0.01 microM, and, therefore, were selected for further evaluation for in vivo antitumor activity.
authors.affiliation: School of Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan. yeloch@cc.kmu.edu.tw
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Chao-Ho
authors.initials: CH
authors.lastname: Chung
authors.forename: I-Li
authors.initials: IL
authors.lastname: Chen
authors.forename: Po-Hsu
authors.initials: PH
authors.lastname: Chen
authors.forename: Haw-Yaun
authors.initials: HY
authors.lastname: Jeng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines; D015363:Quinolones