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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-La and H-Lb, respectively. Compared with H-La, the ligand H-Lb more strongly inhibited telomerase activity in the SK-OV-3 cells model.

SUBMITTER: Wei ZZ

PROVIDER: S-EPMC6274343 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other

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Oxoisoaporphine as Potent Telomerase Inhibitor.

Wei Zu-Zhuang ZZ Qin Qi-Pin QP Chen Jia-Nian JN Chen Zhen-Feng ZF

Molecules (Basel, Switzerland) 20161114 11

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 dock ...[more]

PMID: 27854257

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