Synthesis, characterization, in vitro SAR and in vivo evaluation of N, N′bisnaphthylmethyl 2-alkyl substituted imidazolium salts against NSCLC

被引：8

作者：

DeBord, Michael A. ^{[1
]}

Southerland, Marie R. ^{[1
]}

Wagers, Patrick O. ^{[1
]}

Tiemann, Kristin M. ^{[2
,3
]}

Robishaw, Nikki K. ^{[1
]}

Whiddon, Kyle T. ^{[1
]}

Konopka, Michael C. ^{[1
]}

Tessier, Claire A. ^{[1
]}

Shriver, Leah P. ^{[1
,4
]}

Paruchuri, Sailaja ^{[1
]}

Hunstad, David A. ^{[2
,3
]}

Panzner, Matthew J. ^{[1
]}

Youngs, Wiley J. ^{[1
]}

机构：

[1] Univ Akron, Dept Chem, Akron, OH 44325 USA

[2] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA

[4] Univ Akron, Dept Biol, Akron, OH 44325 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 04期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

Imidazolium salt; Anti-cancer; Anti-tumor; Lung cancer; Cyclodextrin; ANTITUMOR-ACTIVITY; CYCLODEXTRINS; CISPLATIN; DESIGN;

D O I：

10.1016/j.bmcl.2017.01.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Alkyl- and N,N'-bisnaphthyl-substituted imidazolium salts were tested in vitro for their anti-cancer activity against four non-small cell lung cancer cell lines(NCI-H460, NCI-H1975, HCC827, A549). All compounds had potent anticancer activity with 2 having IC50 values in the nanomolar range for three of the four cell lines, a 17-fold increase in activity against NCI-H1975 cells when compared to cisplatin. Compounds 1-4 also showed high anti-cancer activity against nine NSCLC cell lines in the NCI-60 human tumor cell line screen. In vitro studies performed using the Annexin V and JC-1 assays suggested that NCI H460 cells treated with 2 undergo an apoptotic cell death pathway and that mitochondria could be the cellular target of 2 with the mechanism of action possibly related to a disruption of the mitochondrial membrane potential. The water solubilities of 1-4 was over 4.4 mg/mL using 2-hydroxypropyl-beta-cyclodextrin as a chemical excipient, thereby providing sufficient solubility for systemic administration. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：764 / 775

页数：12

共 29 条

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