Screening of G-quadruplex ligands from Macleaya cordata extract by contrast ultrafiltration with liquid chromatography-mass spectrometry and molecular docking / 中国中药杂志

G-quadruplex DNA has become an important target for tumor therapy and anti-tumor development. Modern pharmacology has proved that Macleaya cordata has anti-inflammatory, antibacterial, anti-tumor and other pharmacological effects. Affinity ultrafiltration method can screen active ingredients from compounds rapidly, but G-quadruplex DNA ligands are difficult to dissociate, which is a key step in conventional ultrafiltration method. In this paper, the filtrates after ultrafiltration were determined by HPLC-MS in substitution. The peaks with 20% reduction of MS response from the incubation vs control were considered to be ligand components to G-quadruplex. Two of the peaks with the relative abundance above 30% were identified as sanguinarine(SAN) and chelerine(CHE). Their circular dichroism conformations further proved that SAN and CHE are active ligands of HT4. In addition, another two gradients with high relative abundance were identified as protopine(PRO) and allpcryprotopine(ALL). The binding rate of SAN, CHE, PRO and ALL was calculated according to the HPLC-MS results, and the results showed a consistency with that of the molecular docking method. The proposed method can be used to screen active components from mixture.

Design, synthesis and biological activities of novel 3,6-diamide xanthones / 药学学报

A series of novel xanthones with terminal amine substituents at xanthone's C3 and C6 positions were designed and synthesized as potential ligands for telomeric G-quadruplex DNA. All the compounds in this series were bound to telomeric G-quadruplex in a "thread intercalation" manner that illustrated both in molecular docking and spectrometric studies. Among them, 10c and 10d showed better binding abilities and specific affinity toward G-quadruplex DNA HTG21 over ctDNA in the fluorescence assay. The antiproliferative activities of four screened compounds were examined in three cancer cells by MTT in vitro, and their inhibitory effects were observed at low micromolar ranges. In addition, the PCR stop assay demonstrated that 10c and 10d effectively inhibited the amplification ability of telomerase.

Study of human telomere G4-DNA stabilizers / 中国药理学通报

Telomere maintenance plays a critical role in cancer progression.Approximately 85% human cancer cells maintain their telomere length through activation of telomerase.Other 15%of cancers maintain telomere length independently of telom-erase by alternative lengthening of telomeres (ALT)pathway. Both events are equally important for telomere length mainte-nance of cancer cells.Human telomere consists of a series of G rich DNA sequences,which could form G-quadruplex.The for-mation of this structure can block the extension of telomeres by telomerase or ALT,resulting in cancer cell death.Thereby,G-quadruplex has been one of the focuses of anticancer therapy in recent years.This review focuses on the latest progress of G-quadruplex stabilizers.