合成与构效关系；某些强效抗癌苯甲脒衍生物的探索
Synthesis and Structure-Activity Relationship; Exploration of some Potent Anti-Cancer Phenyl Amidrazone Derivatives.
作者信息
Habashneh Almeqdad Y, El-Abadelah Mustafa M, Bardaweel Sanaa K, Taha Mutasem O
机构信息
Faculty of Science, Chemistry Department, The University of Jordan, Amman, Jordan.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, The University of Jordan, Amman, Jordan.
出版信息
Med Chem. 2018;14(5):468-477. doi: 10.2174/1573406414666171204143157.
BACKGROUND
Amidrazones have been reported to have significant anti-tumor properties against several cancer cell lines.
OBJECTIVES
The current project aims to profile the structure-anticancer activity relationship of phenyl-amidrazons.
METHODS
Fifteen phenyl-amidrazone-piperazine derivatives were prepared and tested against four cancer cell lines (leukemia, prostate, breast and colon cancers).
RESULTS
Six compounds illustrated low micromolar anticancer IC50 values, while the remaining compounds were either inactive or of moderate potencies. All compounds were virtually nontoxic against normal fibroblast cells.
CONCLUSION
Docking into the oncogenic kinase bcr/abl illustrated the critical importance of (i) phalogen substituent on the ligand's phenyl ring and (ii) the presence of positive ionizable moiety at the ligand's piperazine fragment for anticancer activity.
背景
据报道，脒腙对多种癌细胞系具有显著的抗肿瘤特性。
目的
当前项目旨在剖析苯基脒腙的结构-抗癌活性关系。
方法
制备了15种苯基脒腙-哌嗪衍生物，并针对四种癌细胞系（白血病、前列腺癌、乳腺癌和结肠癌）进行测试。
结果
六种化合物表现出低微摩尔浓度的抗癌IC50值，而其余化合物要么无活性，要么活性中等。所有化合物对正常成纤维细胞几乎无毒。
结论
对接致癌激酶bcr/abl表明，（i）配体苯环上的卤素取代基和（ii）配体哌嗪片段上存在可离子化的正电荷部分对抗癌活性至关重要。
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