Synthesis of Novel Pyrazole Derivatives and Their Tumor Cell Growth Inhibitory Activity

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2019 Jan 16

PMID 30642134

Citations 4

Authors

Ying-Jie Cui

Long-Qian Tang

Cheng-Mei Zhang

Zhao-Peng Liu

Affiliations

Soon will be listed here.

Abstract

To find novel antitumor agents, a series of 1-benzofuro[3,2-]pyrazole derivatives were designed and synthesized. The treatment of 6-methoxybenzofuran-3(2)-one with LiHMDS in anhydrous tetrahydrofuran (THF) followed by reaction with 3-substitued phenyl isothiocyanate gave the thioamide intermediates, which underwent condensation with hydrazine monohydrate in dioxane/EtOH (1:1) to provide the benzofuropyrazole derivatives ⁻ as well as the unexpected pyrazole derivatives ⁻. In tumor cell growth inhibitory assay, all the benzofuropyrazole derivatives were not active against the breast tumor MCF-7 cell, only was highly active and more potent than ABT-751 against the leukemia K562 (GI = 0.26 μM) and lung tumor A549 cells (GI = 0.19 μM), while other benzofuropyrazoles showed very weak inhibitory activity. In contrast, the pyrazoles were in general more potent than the benzofuropyrazoles ⁻. Compound exhibited a similar tendency to that of with high potency against K562 and A549 cells but weak effects on MCF-7 cell. Both pyrazoles and exhibited high inhibitory activities against K562, MCF-7 and A549 cells. The most active compound was much more potent than ABT-751 against K562 and A549 cells with GI values of 0.021 and 0.69 M, respectively. Moreover, was identified as a novel tubulin polymerization inhibitor with an IC of 7.30 M.

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