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Unsymmetrically substituted benzimidazolium based Silver(I)-N-heterocyclic carbene complexes: Synthesis, characterization and in vitro anticancer study against human breast cancer and colon cancer
Journal of Saudi Chemical Society ( IF 5.8 ) Pub Date : 2019-03-23 , DOI: 10.1016/j.jscs.2019.03.002
Aqsa Habib , Mansoureh Nazari V. , Muhammad Adnan Iqbal , Haq Nawaz Bhatti , M.B. Khadeer Ahmed , A.M.S. Abdul Majid

The promising biomedical applications of silver complexes stimulated the researchers to test these compounds against cancer. The present research work was designed to achieve this goal. In this work, a series of 5-methyl benzimidazole based N-Heterocyclic carbene ligands and respective silver(I) complexes were synthesized and tested on cancer cell lines to assess their anticancer activity. Unsymmetrically substituted benzimidazole was found unique in its reactivity and generation of a single product during NHC ligand formation was only possible after two successive alkylations with same alkyl halide. The corresponding Ag(I)-NHC adducts were obtained by in situ deprotonation of the NHC ligands. Synthesized compounds were characterized by various physcio-chemical and spectroscopic methods. Single crystal X-ray diffraction study of complex 7 revealed its mononuclear structure. Preliminary in vitro anticancer study of azolium salts and respective Ag(I)-NHC complexes against human breast cancer (MDA-MB-231), colon cancer (HCT-116) and normal endothelial cells (EA.hy926) cells revealed that all the compounds are more cytotoxic to cancer cells than normal cells and the complexes are relatively more potent compared to the corresponding NHC ligands. It was found that increased chain length and presence of methyl substituent on benzimidazole ring enhance the biopotency of Ag(I)-NHC complexes. The synthesized compounds were further studied for pro-apoptotic mechanism of action via Rhodamine 123 test. The tested compounds were found to induce apoptosis via extrinsic mitochondrial pathway.



中文翻译:

不对称取代的苯并咪唑基银(I)-N-杂环卡宾配合物:针对人类乳腺癌和结肠癌的合成,表征和体外抗癌研究

银配合物的有前途的生物医学应用刺激了研究人员测试这些化合物的抗癌性。当前的研究工作旨在实现这一目标。在这项工作中,合成了一系列基于5-甲基苯并咪唑的N-杂环卡宾配体和相应的银(I)配合物,并在癌细胞系上进行了测试,以评估其抗癌活性。发现不对称取代的苯并咪唑具有独特的反应活性,只有在使用相同的烷基卤连续两次烷基化之后,才能在NHC配体形成过程中生成单一产物。通过原位获得相应的Ag(I)-NHC加合物NHC配体的去质子化。通过各种物理化学和光谱方法对合成的化合物进行了表征。配合物7的单晶X射线衍射研究揭示了其单核结构。初步体外偶氮盐和相应的Ag(I)-NHC复合物对人乳腺癌(MDA-MB-231),结肠癌(HCT-116)和正常内皮细胞(EA.hy926)细胞的抗癌研究表明,所有化合物均与正常细胞相比,它对癌细胞具有细胞毒作用,并且与相应的NHC配体相比,复合物的效力相对更高。发现增加的链长和在苯并咪唑环上甲基取代基的存在增强了Ag(I)-NHC复合物的生物效能。通过若丹明123试验进一步研究了合成的化合物的促凋亡作用机理。发现所测试的化合物通过外在的线粒体途径诱导细胞凋亡。

更新日期:2019-03-23
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