title: Syntheses and cell-based phenotypic screen of novel 7-amino pyrido[2,3-d]pyrimidine-6-carbonitrile derivatives as potential antiproliferative agents.
abstract: A series of N-3-substituted 7-aminopyrido[2,3-d]pyrimidin-6-carbonitrile derivatives was readily synthesized and their anti-proliferative activities on five types of tumor cells were evaluated through a cell-based phenotypic screening approach. Compound 3k was found to be potent on human colon cancer SW620 cells with an IC(50) value of 12.5 mM. Structural optimization of compound 3k led to compound 4a with improved anti-proliferative potency on SW620 cells with an IC(50) value of 6.9 mM. Further cell-cycle analyses suggested that compound 4a induced apoptosis of SW620 cells in a concentration-dependent manner.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Ang
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: Yang
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Yang
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Lin
authors.forename: Hua-Cheng
authors.initials: HC
authors.lastname: Yang
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Pi
authors.forename: Zi-Cheng
authors.initials: ZC
authors.lastname: Li
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Zhao
authors.forename: You-Fu
authors.initials: YF
authors.lastname: Luo
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D011743:Pyrimidines