Bioorganic & Medicinal Chemistry Letters 2010-07-15

Synthesis and molecular docking studies of novel 2-chloro-pyridine derivatives containing flavone moieties as potential antitumor agents.

Xin-Hua Liu, Hui-Feng Liu, Xu Shen, Bao-An Song, Pinaki S Bhadury, Hai-Liang Zhu, Jin-Xing Liu, Xing-Bao Qi

Index: Bioorg. Med. Chem. Lett. 20 , 4163-4167, (2010)

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Abstract

A series of novel 2-chloro-pyridine derivatives containing flavone, chrome or dihydropyrazole moieties as potential telomerase inhibitors were synthesized. The bioassay tests showed that compounds 6e and 6f exhibited some effect against gastric cancer cell SGC-7901 with IC(50) values of 22.28+/-6.26 and 18.45+/-2.79 microg/mL, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results showed that compound 6e can strongly inhibit telomerase with IC(50) value of 0.8+/-0.07 microM. Docking simulation was performed to position compound 6e into the active site of telomerase (3DU6) to determine the probable binding model.2010 Elsevier Ltd. All rights reserved.


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