title: Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: synthesis and anticancer activity.
abstract: A series of novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives were designed and synthesized. All compounds have been screened for their antiproliferative activity against MGC-803, SGC-7901 and Bcap-37 cell lines in vitro. The results revealed that compounds 8a, 8c and 8e exhibited strong inhibitory activity against MGC-803 cell line. The flow cytometric analysis result showed that compound 8e could inhibit MGC-803 proliferation. Some title compounds were tested against telomerase, and compound 8e showed the most potent inhibitory activity with IC50 value at 1.02 ± 0.08 μM. The docking simulation of compound 8e was performed to get the probable binding model, among them, LYS 189, LYS 372, LYS 249 and ASP 254 may be the key residues for the telomerase activity.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China. Electronic address: sjb0616@126.com.
authors.forename: Jing Bo
authors.initials: JB
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Wen Jian
authors.initials: WJ
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Xing Bao
authors.initials: XB
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: xhliuhx@163.com.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D011743:Pyrimidines; C030986:pyrimidine
keywords: Anticancer activity; Pyrazole-5-carboxamide; Synthesis; Telomerase