title: Oxoisoaporphine as Potent Telomerase Inhibitor.
abstract: Two compounds previously isolated from traditional Chinese medicine,Menispermum dauricum(DC), 6-hydroxyl-oxoisoaporphine (H-La), and 4,6-di(2-pyridinyl)benzo[h]isoindolo[4,5,6-de]quinolin-8(5H)-one (H-Lb), were known to have in vitro antitumor activity and to selectively bind human telomeric, c-myc, and bcl-2 G-quadruplexes (G4s). In this study, the binding properties of these two compounds to telomerase were investigated through molecular docking and telomeric repeat amplication protocol and silver staining assay (TRAP-silver staining assay). The binding energies bound to human telomerase RNA were calculated by molecular docking to be -6.43 and -9.76 kcal/mol for H-Laand H-Lb, respectively. Compared with H-La, the ligand H-Lbmore strongly inhibited telomerase activity in the SK-OV-3 cells model.
authors.affiliation: State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. weizuzhuang@126.com.
authors.forename: Zu-Zhuang
authors.initials: ZZ
authors.lastname: Wei
authors.affiliation: State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. qinqipin2007@126.com.
authors.forename: Qi-Pin
authors.initials: QP
authors.lastname: Qin
authors.affiliation: State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. cjn288@sina.com.
authors.forename: Jia-Nian
authors.initials: JN
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, China. chenzf@gxnu.edu.cn.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001060:Aporphines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D054856:G-Quadruplexes / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D012313:RNA / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001060:Aporphines; D004791:Enzyme Inhibitors; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase
keywords: molecular docking; oxoisoaporphine; telomerase