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设计、合成及含 NHC-Au(I) 配合物和咔唑部分的多靶点杂化分子的生物评价。

Design, synthesis and biological evaluation of multitarget hybrid molecules containing NHC-Au(I) complexes and carbazole moieties.

机构信息

Department of Chemistry and Biology "A. Zambelli", University of Salerno, Via Giovanni Paolo II 132, I-84084, Fisciano, SA, Italy.

Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Via Pietro Bucci, I-87036, Arcavacata di Rende, CS, Italy.

出版信息

Eur J Med Chem. 2024 Nov 5;277:116757. doi: 10.1016/j.ejmech.2024.116757. Epub 2024 Aug 9.

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(NHCs)是快速高效药物设计的合适配体,因为它们具有易于化学修饰和可结合多个取代基的优点,包括过渡金属,例如金衍生物。金-NHC 配合物具有多种生物活性,被证明是有前途的抗癌药物候选物。此外,咔唑衍生物具有多种药理学特性,如抗癌、抗菌、抗炎和抗精神病。在后者中,N-硫代烷基咔唑已被证明通过抑制人拓扑异构酶来抑制破坏核 DNA 的癌细胞。在此,我们报告了九种新型杂化分子的设计、合成和生物学评价,其中将 NHC-Au(I) 配合物和 N- 烷基硫代咔唑连接在一起,以获得新型的多靶生物试剂。我们证明了先导杂化配合物具有抗癌、抗炎和抗氧化特性,具有作为治疗多种疾病(包括癌症)不同方面的有用工具的高潜力。

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