Selg Christoph, Grell Toni, Brakel Alexandra, Andrews Philip C, Hoffmann Ralf, Hey-Hawkins Evamarie
Institute of Bioanalytical Chemistry, Centre for Biotechnology and Biomedicine, Leipzig University, Deutscher Platz 5, 04103, Leipzig, Germany.
Department of Chemistry, University of Milano, Via Camillo Golgi 19, 20133, Milano, Italy.
Chempluschem. 2024 Jun;89(6):e202300759. doi: 10.1002/cplu.202300759. Epub 2024 Feb 13.
This study proposes an innovative strategy to enhance the pharmacophore model of antimicrobial bismuth thiolato complex drugs by substituting hydrocarbon ligand structures with boron clusters, particularly icosahedral closo-dicarbadodecaborane (CBH, carboranes). The hetero- and homoleptic mercaptocarborane complexes BiPhL (1) and BiL (2) (L=9-S-1,2-CBH) were prepared from 9-mercaptocarborane (HL) and triphenylbismuth. Comprehensive characterization using NMR, IR, MS, and XRD techniques confirmed their successful synthesis. Evaluation of antimicrobial activity in a liquid broth microdilution assay demonstrated micromolar to submicromolar minimum inhibitory concentrations (MIC) suggesting high effectiveness against S. aureus and limited efficacy against E. coli. This study highlights the potential of boron-containing bismuth complexes as promising antimicrobial agents, especially targeting Gram-positive bacteria, thus contributing to the advancement of novel therapeutic approaches.
本研究提出了一种创新策略,通过用硼簇(特别是二十面体闭式-二碳十二硼烷(CBH,碳硼烷))取代烃类配体结构,来增强抗微生物硫醇铋配合物药物的药效团模型。由9-巯基碳硼烷(HL)和三苯基铋制备了杂配和同配的巯基碳硼烷配合物BiPhL(1)和BiL(2)(L = 9-S-1,2-CBH)。使用NMR、IR、MS和XRD技术进行的综合表征证实了它们的成功合成。在液体肉汤微量稀释试验中对抗菌活性的评估表明,其最低抑菌浓度(MIC)为微摩尔至亚微摩尔,表明对金黄色葡萄球菌具有高效性,而对大肠杆菌的效力有限。本研究突出了含硼铋配合物作为有前景的抗微生物剂的潜力,特别是针对革兰氏阳性菌,从而有助于推动新型治疗方法的发展。