title: Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as potential anti-tumor agents.
abstract: Three series of novel 4-benzothiazole amino quinazolines Dasatinib derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro cytotoxic activity by the MTT-based assay against 6 human cancer cell lines. Compared with the parental Dasatinib, most of the new compounds, especially 2, 4, 6-trimethylaniline series (3), demonstrated significant inhibitory activities against six cell lines. Furthermore, the target compounds were screened for Src and Abl kinase inhibitory activity. Among them, 1a, 1f and 3a-3f are more potential dual Src/Abl kinase inhibitors. Thus they may be promising lead compounds to be developed as an alternative for current Dasatinib therapy or for Imatinib-resistant patients, potentially via simultaneously blocking multiple RTK signaling pathways.
authors.affiliation: School of Chemistry and Chemical Engineering, Institute of Pharmaceutical Engineering, Southeast University, 87 Dingjiaqiao, Nanjing, Jiangsu 210096, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cai
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wu
authors.forename: Junqing
authors.initials: J
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Zong
authors.forename: Min
authors.initials: M
authors.lastname: Ji
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D000069439:Dasatinib; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D008956:Models, Chemical; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry*; D020298:U937 Cells; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011799:Quinazolines; D013844:Thiazoles; D016315:Proto-Oncogene Proteins c-abl; D019061:src-Family Kinases; C005465:benzothiazole; D000069439:Dasatinib