Half-sandwich triazolato Rh(III) compound of pyridylbenzimidazole ligand with cell selective toxicity towards Cryptococcus neoformans

Recently, screening attempts for potential antimicrobial drugs based on metal-based compounds have shown an unpredictably high hit rate for some classes of organometallic compounds (9.9%) com-pared to some organic compounds (0.87%) submitted to the same assays. Herein, we report the influ-ence of the axial ligand (X = Cl and triazolate(COOC2H5,CF3)) on the antimicrobial activity of [Rh-2(X)(2)(eta(5)-C5Me5)(2)L](2+) (L = 1,1'-(Hexane-1,6-diyl)bis[2-(pyridin-2-yl)1H-benzimidazole]) against some bacterial and fungal pathogens as well as healthy cells. The compatibility with red blood cells was also examined. The stability of the compounds in presence of a model lysozyme protein was followed to gather insight into the activation profiles . Triazolate compound was prepared under a mild reaction via catalyst-free [3 + 2] cycloaddition reaction of azide analogue with 4,4,4-trifluoro-2-butynoic acid ethyl ester. While triazolate complex exhibited higher antifungal activity (MIC = 4.8-9.7 mu M) against C. neoformans than Fluconazole (MIC = 26.1 mu M), the chloro analogue dispalyed no activity towards the same microorganism. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

Screening for potential antimicrobial drugs using metal-based compounds has shown unexpectedly high hit rates compared to organic compounds. The influence of the axial ligand on the antimicrobial activity against various pathogens and healthy cells was studied, along with compatibility with red blood cells. The stability of the compounds in the presence of a lysozyme protein was also examined for insight into activation profiles.