title: Novel dihydropyrazole-chromen: Design and modulates hTERT inhibition proliferation of MGC-803.
abstract: Dominant-negative mutant of telomerase hTERT was demonstrated to show selective anticancer effects in tumor cells. But, an effective hTERT inhibitor with high selectivity has not been developed so far. Focused on hTERT, a novel dihydropyrazole-chromen (13k) controlling hTERT was designed. Title compound 13k occupied high antiproliferative activity against MGC-803 cells with IC50 value 1.41 μM, but it manifested obvious un-toxic effect on human normal gastric mucosa cells with the IC50 2.3 mM. Treated with compound 13k, the further inhibition mechanisms by modulating hTERT was explored, the results showed that expression of hTERT was clearly modulated, and then β-catenin activation was decreased, thereby the expression of downstream signaling molecules including c-myc and cyclin D1 was modulated, leading to inhibition MGC-803 cells proliferation.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China; The Fourth Affiliated Hospital of Anhui Medical University, Hefei, 230022, PR China.
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China.
authors.forename: Xiao Qin
authors.initials: XQ
authors.lastname: Wu
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: Jing Bo
authors.initials: JB
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China. Electronic address: lijun@ahmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China. Electronic address: xhliuhx@163.com.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D016271:Proto-Oncogene Proteins c-myc; D011720:Pyrazoles; D051176:beta Catenin; C509186:TERT protein, human; D019098:Telomerase
keywords: Dihydropyrazole-chromen; Selective anticancer activity; TERT modulator; Telomerase