title: Synthesis and biological activity of 2,5-diaryl-3-methylpyrimido[4,5-c]quinolin-1(2H)-one derivatives.
abstract: A series of 2,5-diaryl-3-methylpyrimido[4,5-c]quinolin-1(2H)-ones (7-30), variously substituted at the 2- and 5-phenyl moieties, were synthesized and evaluated for their in vitro cytotoxic activity against a PC3 cancer cell line. Cytotoxicity data revealed that the type of substituent as well as substitution pattern have variable influence on cytotoxic activity. Among the compounds tested, compounds (9), (13), (18), (19), and (23) demonstrated appreciable cytotoxic activity with mean IC(50) values of 2.0, 1.4, 1.6, 2.2, and 1.9microM, respectively. Methyl substitution at the 2-phenyl ring was found to yield the least active compounds. Two of the most potent compounds (13) and (18) were further investigated for inhibition of tubulin polymerization and found to have no activity at the concentrations used in the assay.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. kametwally@hotmail.com
authors.forename: Kamel
authors.initials: K
authors.lastname: Metwally
authors.forename: Omar
authors.initials: O
authors.lastname: Aly
authors.forename: Enayat
authors.initials: E
authors.lastname: Aly
authors.forename: Abhijit
authors.initials: A
authors.lastname: Banerjee
authors.forename: Rudravajhala
authors.initials: R
authors.lastname: Ravindra
authors.forename: Susan
authors.initials: S
authors.lastname: Bane
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D016588:Anticarcinogenic Agents; D011743:Pyrimidines; D011804:Quinolines; C030986:pyrimidine