Evaluation of novel aryloxyalkyl derivatives of imidazole and 1,2,4-triazole as heme oxygenase-1 (HO-1) inhibitors and their antitumor properties
Evaluation of novel aryloxyalkyl derivatives of imidazole and 1,2,4-triazole as heme oxygenase-1 (HO-1) inhibitors and their antitumor properties
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DOI：
10.1016/j.bmc.2013.06.040
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Sorrenti, Valeria
中科院分区：
文献类型：
--
作者：
Salerno, Loredana;Pittala, Valeria;Sorrenti, Valeria
设计并合成了咪唑和1,2,4-三唑的芳基烷基衍生物17-31，作为血红素加氧酶-1 （HO-1）和血红素加氧酶-2 （HO-2）的抑制剂。其中一些化合物被发现是HO-1的良好抑制剂，特别是那些以咪唑基为偶氮基，以3-溴或4-碘苯基为芳基的化合物。选择了最有效的化合物6和30，并在LAMA-84 R细胞系模型中研究了它们的抗肿瘤特性，这些细胞过表达HO-1并对甲磺酸伊马替尼（IM）耐药，imatinib是一种酪氨酸激酶抑制剂，用于治疗多种类型的癌症，最显著的是费城染色体阳性（Ph+）慢性粒细胞白血病（CML）。结果表明，6和30均能使lama - 84r细胞株对IM的抗肿瘤特性增敏。(C) 2013 Elsevier Ltd.版权所有。
A novel series of aryloxyalkyl derivatives of imidazole and 1,2,4-triazole, 17-31, was designed and synthesized as inhibitors of heme oxygenase-1 (HO-1) and heme oxygenase-2 (HO-2). Some of these compounds were found to be good inhibitors of HO-1, in particular those carrying an imidazole moiety as azolyl group and a 3-bromo or 4-iodophenyl as aryl moiety. The most potent compounds 6 and 30 were selected and studied for their antitumor properties in a model of LAMA-84 R cell line overexpressing HO-1 and resistant to imatinib mesylate (IM), a tyrosine-kinase inhibitor used in the treatment of multiple types of cancer, most notably Philadelphia Chromosome positive (Ph+) Chronic Myelogenous Leukemia (CML). Results show that both 6 and 30 sensitized LAMA-84 R cell line to antitumor properties of IM. (C) 2013 Elsevier Ltd. All rights reserved.