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.
引用
收藏
页码：83 / 87
页数：5
相关论文
共 24 条
  • [1] Prospective identification of tumorigenic breast cancer cells
    Al-Hajj, M
    Wicha, MS
    Benito-Hernandez, A
    Morrison, SJ
    Clarke, MF
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) : 3983 - 3988
  • [2] Understanding the cancer stem cell
    Bomken, S.
    Fiser, K.
    Heidenreich, O.
    Vormoor, J.
    [J]. BRITISH JOURNAL OF CANCER, 2010, 103 (04) : 439 - 445
  • [3] Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell
    Bonnet, D
    Dick, JE
    [J]. NATURE MEDICINE, 1997, 3 (07) : 730 - 737
  • [4] Aldehyde Dehydrogenase 1-Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer
    Charafe-Jauffret, Emmanuelle
    Ginestier, Christophe
    Iovino, Flora
    Tarpin, Carole
    Diebel, Mark
    Esterni, Benjamin
    Houvenaeghel, Gilles
    Extra, Jean-Marc
    Bertucci, Francois
    Jacquemier, Jocelyne
    Xerri, Luc
    Dontu, Gabriela
    Stassi, Giorgio
    Xiao, Yi
    Barsky, Sanford H.
    Birnbaum, Daniel
    Viens, Patrice
    Wicha, Max S.
    [J]. CLINICAL CANCER RESEARCH, 2010, 16 (01) : 45 - 55
  • [5] Strategies to target HER2/neu overexpression for cancer therapy
    Chen, JS
    Lan, K
    Hung, MC
    [J]. DRUG RESISTANCE UPDATES, 2003, 6 (03) : 129 - 136
  • [6] Synthesis, cytotoxicity, and antitumor activity of copper(II) and iron(II) complexes of 4N-azabicyclo[3.2.2]nonane thiosemicarbazones derived from acyl diazines
    Easmon, J
    Pürstinger, G
    Heinisch, G
    Roth, T
    Fiebig, HH
    Holzer, W
    Jäger, W
    Jenny, M
    Hofmann, J
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (13) : 2164 - 2171
  • [7] ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome
    Ginestier, Christophe
    Hur, Min Hee
    Charafe-Jauffret, Emmanuelle
    Monville, Florence
    Dutcher, Julie
    Brown, Marty
    Jacquemier, Jocelyne
    Viens, Patrice
    Kleer, Celina G.
    Liu, Suling
    Schott, Anne
    Hayes, Dan
    Birnbaum, Daniel
    Wicha, Max S.
    Dontu, Gabriela
    [J]. CELL STEM CELL, 2007, 1 (05) : 555 - 567
  • [8] Synthesis and structure-activity relationships of parasiticidal thiosemicarbazone cysteine protease inhibitors against Plasmodium falciparum, Trypanosoma brucei, and Trypanosoma cruzi
    Greenbaum, DC
    Mackey, Z
    Hansell, E
    Doyle, P
    Gut, J
    Caffrey, CR
    Lehrman, J
    Rosenthal, PJ
    McKerrow, JH
    Chibale, K
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (12) : 3212 - 3219
  • [9] Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells
    Ho, Maria M.
    Ng, Alvin V.
    Lam, Stephen
    Hung, Jaclyn Y.
    [J]. CANCER RESEARCH, 2007, 67 (10) : 4827 - 4833
  • [10] Thiosemicarbazones of formyl benzoic acids as novel potent inhibitors of estrone sulfatase
    Juetten, Peter
    Schumann, Winfried
    Haertl, Albert
    Dahse, Hans-Martin
    Graefe, Udo
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (15) : 3661 - 3666
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