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N-Heterocyclic Carbene (NHC) Silver Complexes as Versatile Chemotherapeutic Agents Targeting Human Topoisomerases and Actin
ChemMedChem ( IF 3.4 ) Pub Date : 2022-07-29 , DOI: 10.1002/cmdc.202200345
Annaluisa Mariconda 1 , Domenico Iacopetta 2 , Marco Sirignano 3 , Jessica Ceramella 2 , Chiara Costabile 3 , Michele Pellegrino 2 , Camillo Rosano 4 , Alessia Catalano 5 , Carmela Saturnino 1 , Hussein El-Kashef 6 , Stefano Aquaro 2 , Maria Stefania Sinicropi 2 , Pasquale Longo 3
Affiliation  

It is known that most bioactive anticancer molecules do not target a single protein but exert pleiotropic effects, simultaneously affecting multiple pathways. We designed and synthesized a new series of silver N-heterocyclic carbene (NHC) complexes that are active against two human breast cancer cell lines and that show multiple target actions by inhibiting human topoisomerase I and II activity in vitro and interfering with cytoskeleton dynamics. The antimicrobial activity of these silver complexes was also studied against Gram-positive/negative bacteria. Compounds 2 and 6 inhibit human topoisomerases I and II and actin polymerization. Compound 6 also induces F-actin depolymerization.

中文翻译:

N-杂环卡宾 (NHC) 银络合物作为靶向人类拓扑异构酶和肌动蛋白的多功能化疗剂

众所周知,大多数具有生物活性的抗癌分子并不针对单一蛋白质,而是发挥多效性作用,同时影响多种途径。我们设计并合成了一系列新的银N-杂环卡宾 (NHC) 复合物,这些复合物对两种人类乳腺癌细胞系具有活性,并通过在体外抑制人类拓扑异构酶 I 和 II 活性并干扰细胞骨架动力学显示出多种靶向作用。还研究了这些银配合物对革兰氏阳性/阴性细菌的抗菌活性。化合物26抑制人拓扑异构酶 I 和 II 以及肌动蛋白聚合。化合物6还诱导 F-肌动蛋白解聚。
更新日期:2022-07-29
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