title: Synthesis and antiproliferative evaluation of certain pyrido[3,2-g]quinoline derivatives.
abstract: The present report describes the synthesis and evaluation of tricyclic pyrido[3,2-g]quinoline derivatives in which an additional pyridine ring is linearly fused on the antibacterial quinoline-3-carboxylic acid. Among them, only diethyl 4,6-diamino-10-methylpyrido[3,2-g]quinoline-3,7-dicarboxylate (9a) and diethyl 4,6-bis-(3-dimethylaminopropylamino)-10-methylpyrido[3,2-g]quinoline-3,7-dicarboxylate (9d) were able to completely inhibit cell proliferation of MCF7 (Breast), NCI-H460 (Lung), and SF-268 (CNS) implying either amino or dimethylaminopropyl moiety at C-4 and C-6 positions is crucial for the antiproliferative activity of pyrido[3,2-g]quinoline derivatives. Compounds 9a-9d were further evaluated for their activity against the growth of MCF-7 and two prostate cancer cell lines, LNCaP and PC-3. Results indicated the antiproliferative activity decreased in an order 9d>9a>>9b and 9c. Compound 9d was the most cytotoxic with an IC50 value of 5.63 and 3.96 microM, respectively, against LNCaP and MCF-7. Flow cytometric analyses revealed that growth inhibition of LNCaP by 9d was due to cell cycle arrest in G1 phase, and followed by apoptosis.
authors.affiliation: Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Li
authors.forename: Yeh-Long
authors.initials: YL
authors.lastname: Chen
authors.forename: Chihuei
authors.initials: C
authors.lastname: Wang
authors.forename: Cherng-Chyi
authors.initials: CC
authors.lastname: Tzeng
mesh_terms: 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; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D050256:Antimitotic Agents; D011725:Pyridines; D011804:Quinolines