title: Synthesis and antitumor activity of novel 4-(2-fluorophenoxy)quinoline derivatives bearing the 4-oxo-1,4-dihydroquinoline-3-carboxamide moiety.
abstract: A series of 4-(2-fluorophenoxy)quinoline derivatives bearing the 4-oxo-1,4-dihydroquinoline-3-carboxamide moiety were designed, synthesized, and evaluated for their in vitro antitumor activity against the H460, HT-29, MKN-45, U87MG, and SMMC-7721 cancer cell lines. Most of the tested compounds showed potent activity and high selectivity toward the HT-29 and MKN-45 cell lines. Furthermore, compounds 21b, 21c, and 21i were further examined for their c-Met kinase activity and exhibited strong efficacy with IC50 values in the single-digit nanomolar range, which was comparable with the positive control foretinib. The most promising compound 21c showed excellent cytostatic activity with IC50 values from 0.01 to 0.53 µM against all tested cell lines, thus being 1.7-2.2 times more active than foretinib.
authors.affiliation: Key Laboratary of Original New Drugs Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
authors.forename: Sai
authors.initials: S
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
authors.forename: Mingze
authors.initials: M
authors.lastname: Qin
authors.forename: Haicheng
authors.initials: H
authors.lastname: Liu
authors.forename: Guangyan
authors.initials: G
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C544515:1,4-dihydroquinoline; D000813:Anilides; D000970:Antineoplastic Agents; C544831:GSK 1363089; D047428:Protein Kinase Inhibitors; D011804:Quinolines; D019859:Proto-Oncogene Proteins c-met
keywords: 4-Oxo-1,4-dihydroquinoline-3-carboxamide moiety; Antitumor activity; Synthesis