Institute of Crystallography (IC) CNR, Via Amendola 122/O, 70126 Bari, Italy.
Department of Biology, University of Naples "Federico II", via Cynthia, 80143 Naples, Italy.
Int J Mol Sci. 2021 Mar 2;22(5):2497. doi: 10.3390/ijms22052497.
The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics. -Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC-carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC-Ag neutral and bis NHC-Ag cationic complexes. Their inhibitor effect on bacterial strains Gram-negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms.
抗菌耐药性的出现是抗菌感染斗争的主要弊端之一,促使研究人员开发新型、更有效、多模式的替代药物。由于缺乏银耐药性,且在低浓度下有效,并且与最常用的抗生素相比毒性较低,因此银及其复合物长期以来一直被用作医学中的抗菌剂。杂环卡宾(NHCs)已被广泛用于配位过渡金属,主要用于催化化学。然而,最近,NHC 配体已被应用于金属在抗癌应用中的载体分子。在本研究中,我们从文献中选择了两种基于吖啶骨架的 NHC-碳烯,并详细研究了非经典吡唑衍生的单 NHC-Ag 中性和双 NHC-Ag 阳离子配合物。评估了它们对革兰氏阴性和阳性菌菌株的抑制作用。含有吖啶发色团的咪唑 NHC 银配合物显示出在极低 MIC 值下的有效性。尽管吡唑 NHC 银配合物的活性不如吖啶 NHC-银配合物,但它们代表了具有抗菌特性的此类化合物的首例。此外,所有复合物均无毒,并且在 4 和 24 小时后对哺乳动物细胞(Hek 系)没有显著的活性。根据我们的实验证据,我们有信心,这种有前途的配合物类别可能成为治疗细菌感染的候选药物的有价值起点,提供巨大的疗效并避免耐药机制的发展。