Abstract：
N-heterocyclic carbenes (NHCs) represent suitable ligands for rapid and efficient drug design, because they offer the advantage of being easily chemically modified and can bind several substituents, including transition metals as, for instance, gold derivatives. Gold-NHC complexes possess various biological activities and were demonstrated good candidates as anticancer drugs. Besides, carbazole derivatives are characterized by various pharmacological properties, such as anticancer, antibacterial, anti-inflammatory, and anti-psychotropic. Amongst the latter, N-thioalkyl carbazoles were proved to inhibit cancer cells damaging the nuclear DNA, through the inhibition of human topoisomerases. Herein, we report the design, synthesis and biological evaluation of nine new hybrid molecules in which NHC-Au(I) complexes and N-alkylthiolated carbazoles are linked together, in order to obtain novel biological multitarget agents. We demonstrated that the lead hybrid complexes possess anticancer, anti-inflammatory and antioxidant properties, with a high potential as useful tools for treating distinct aspects of several diseases, amongst them cancer.
摘要：
N-杂环卡宾（NHC）代表了快速有效药物设计的合适配体，因为它们具有易于化学修饰的优点，并且可以结合多个取代基，包括过渡金属，例如,黄金衍生品。Gold-NHC复合物具有多种生物活性，被证明是抗癌药物的良好候选药物。此外,咔唑衍生物的特点是各种药理学性质，比如抗癌，抗菌，抗炎,和反精神药物。在后者中，N-硫代烷基咔唑被证明可以抑制癌细胞破坏核DNA，通过抑制人类拓扑异构酶。在这里，我们报告设计，九种新的杂化分子的合成和生物学评估，其中NHC-Au（I）配合物和N-烷基硫醇化咔唑连接在一起，以获得新型生物多靶点药物。我们证明了铅杂合复合物具有抗癌作用，抗炎和抗氧化特性，具有很高的潜力作为治疗几种疾病不同方面的有用工具，其中有癌症。
