title: Design and synthesis of novel 2-methyl-4,5-substitutedbenzo[f]-3,3a,4,5-tetrahydro-pyrazolo[1,5-d][1,4]oxazepin-8(7H)-one derivatives as telomerase inhibitors.
abstract: Eight novel 4,5-tetrahydropyrazolo[1,5-d][1,4]oxazepine derivatives have been synthesized and purified to be screened for anticancer activity. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 4a showed the most potent inhibitory activity with IC(50) value at 0.78 ± 0.22 μM. Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1, TERT, phospho-AKT and PI3K/AKT pathway.
authors.affiliation: Key Laboratory of Green Pesticide and Agriculture Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, PR China. xhliuhx@163.com
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Ying-Ming
authors.initials: YM
authors.lastname: Jia
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Song
authors.forename: Zhi-xiang
authors.initials: ZX
authors.lastname: Pang
authors.forename: Song
authors.initials: S
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D018360:Crystallography, X-Ray; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010077:Oxazepines / Q000737:chemistry; D011720:Pyrazoles / Q000737:chemistry; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010077:Oxazepines; D011720:Pyrazoles; D019098:Telomerase