title: Benzophenone-nucleoside derivatives as telomerase inhibitors: Design, synthesis and anticancer evaluation in vitro and in vivo.
abstract: Based on telomerase, thirteen novel phenstatin moiety linked stavudine derivatives (8a∼8e and 11a∼11f) were synthesized. The structures were determined by NMR and TOF-HRMS. The screening results showed that some compounds had better anti-cancer activity in vivo and in vitro. Among them, Compound 8d showed high inhibitory activity against telomerase and showed good antiproliferative activity against SGC-7901 cell with IC50value 0.77 μM by inducing cell cycle arrest at G2 phase. It also could improve SGC-7901 cell apoptosis, mitochondrial membrane potential assay indicated that the dissipation of MMP might participate in apoptosis induced by title compound. In vivo studies showed that compound 8d displayed potent anticancer activity with inhibition tumor growth.
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.
authors.forename: Liu Zeng
authors.initials: LZ
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiou
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 Material Science Chemical Engineering, ChuZhou University, ChuZhou, 239000, PR China.
authors.forename: Hai Pin
authors.initials: HP
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, 230032, PR China; School of Material Science Chemical Engineering, ChuZhou University, ChuZhou, 239000, PR China. Electronic address: xhliuhx@163.com.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Liu
authors.affiliation: School of Pharmacy, China Pharmaceutical University, NanJing, 210009, PR China. Electronic address: qz_yao@yahoo.com.cn.
authors.forename: Qi Zheng
authors.initials: QZ
authors.lastname: Yao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001577:Benzophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D001577:Benzophenones; D004791:Enzyme Inhibitors; D009705:Nucleosides; D019098:Telomerase
keywords: Anticancer activity; Benzophenone-nucleoside derivatives; Inhibitor; Telomerase