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Oxoisoaporphine as Potent Telomerase Inhibitor

Two compounds previously isolated from traditional Chinese medicine, Menispermum dauricum (DC), 6-hydroxyl-oxoisoaporphine (H-L(a)), and 4,6-di(2-pyridinyl)benzo[h]isoindolo[4,5,6-de]quinolin-8(5H)-one (H-L(b)), were known to have in vitro antitumor activity and to selectively bind human telomeric,...

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Detalles Bibliográficos
Autores principales: Wei, Zu-Zhuang, Qin, Qi-Pin, Chen, Jia-Nian, Chen, Zhen-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274343/
https://www.ncbi.nlm.nih.gov/pubmed/27854257
http://dx.doi.org/10.3390/molecules21111534
Descripción
Sumario:Two compounds previously isolated from traditional Chinese medicine, Menispermum dauricum (DC), 6-hydroxyl-oxoisoaporphine (H-L(a)), and 4,6-di(2-pyridinyl)benzo[h]isoindolo[4,5,6-de]quinolin-8(5H)-one (H-L(b)), 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-L(a) and H-L(b), respectively. Compared with H-L(a), the ligand H-L(b) more strongly inhibited telomerase activity in the SK-OV-3 cells model.