Targeting HER-2 over expressed breast cancer cells with 2-cyclohexyl-N-[(Z)-(substituted phenyl/furan-2-yl/thiophene-2-yl)methylidene]hydrazinecarbothioamide

被引：15

作者：

Bhat, Mashooq Ahmad ^{[1
]}

Al-Dhfyan, Abdullah ^{[2
,3
]}

Khan, Azmat Ali ^{[1
]}

Al-Harbi, Nouf ^{[2
]}

Manogaran, P. S. ^{[2
]}

Alanazi, Amer M. ^{[1
]}

Fun, Hoong-Kun ^{[1
,4
]}

Al-Omar, Mohamed A. ^{[1
]}

机构：

[1] King Saud Univ, Dept Pharmaceut Chem, Coll Pharm, Riyadh 11451, Saudi Arabia

[2] King Faisal Specialized Hosp & Res Ctr, Stem Cell & Tissue Re Engn Program, Res Ctr, Riyadh 11211, Saudi Arabia

[3] King Saud Univ, Dept Pharmacol & Toxicol, Coll Pharm, Riyadh 11451, Saudi Arabia

[4] Univ Sains Malaysia, Sch Phys, X Ray Crystallog Unit, Usm Penang 11800, Malaysia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 01期

关键词：

Thiosemicarbazones; Antitumor activity; Breast cancer; HER-2; (2Z)-N-CYCLOHEXYL-2-(3-HYDROXYBENZYLIDINE) HYDRAZINE CARBOTHIOAMIDE; STEM-CELLS; 338.15; K; RESISTANCE; LINES; THIOSEMICARBAZONES; IDENTIFICATION; CHEMOTHERAPY; SOLUBILITY; INHIBITORS;

D O I：

10.1016/j.bmcl.2014.11.009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Cyclohexyl thiosemicarbazone derivatives (C1-14) were synthesized, characterized and evaluated against HER-2 over expressed breast cancer cells. The synthesized compounds were screened in vitro against four breast cancer cell lines; SKBr-3, MCF-7, MDA-MB-468 and MDA-MB-231. All the compounds showed activity against HER-2 over expressed SKBr-3 cells with (IC50 = 25.6 +/- 0.07 mu M-61.6 +/- 0.4 mu M). The most active compounds inhibit ALDH(+) breast cancer stem cells more effectively than the cancer stem cells specific agent Salinomycin. Immunohistochemistry staining also confirmed that these compounds inhibit the expression of HER-2 on SKBr-3 cells. Compound C2 significantly inhibited the cell migration and cell adhesion of breast cancer cell lines. Compound C2 was found to most active compound of this series targeting HER-2 over expressed breast cancer cells. (C) 2014 Elsevier Ltd. All rights reserved.

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收藏

页码：83 / 87

页数：5

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