Molecules (Dec 2024)
Synthesis, Characterization and Antimicrobial Activity of Trimethylantimony(V) Biscyanoximates, a New Family of Antimicrobials
Abstract
Antimicrobial compounds play a critical role in combating microbial infections. However, the emergence of antibiotic and antifungal resistance and the scarcity of new antibiotic developments pose a significant threat and demand the discovery of new antimicrobials for both bacterial and fungal pathogens. Our previous work described the first generation (G1) of organoantimony-based compounds that showed antimicrobial activity against several bacterial and fungal pathogens. Here, we present our efforts in modifying these compounds by replacing the tetraphenyl backbone in G1 compounds with a trimethyl group, thereby generating a new series of compounds we refer to as “generation 2”, G2. In addition to the novel backbone structure, we introduced three new anionic chloro-cyanoxime ligand groups, namely 2,4-diCl-PhCO−, 2,6-diCl-PhCO− and 2Cl-PhCO−, which were found to be biologically active in the past. Nine new compounds of SbMe3L2 composition were obtained in high yields and characterized by NMR, IR spectroscopies, thermogravimetric TG/DSC and X-ray single crystal analyses. The antibacterial activity of the cyanoximates was tested against three bacterial (Pseudomonas aeruginosa PAO1, Escherichia coli S17 and methicillin-resistant Staphylococcus aureus (MRSA) NRS70) and two fungal (Candida albicans strain SC5314 and Cryptococcus neoformans strain H99) pathogens. Two compounds, SbMe3(MCO)2 and SbMe3(2,4-diClPhCO)2, were active against bacterial strains and inhibited the growth of PAO1 and MRSA with MICs of 50 and 100 µg/mL, respectively. Three compounds, SbMe3(MCO)2, SbMe3(ECO)2 and SbMe3(TCO)2, were active against fungal strains and inhibited either one of or both C. albicans and C. neoformans at MICs of 2.6–66.67 μg/mL. In addition, SbMe3(TCO)2 and SbMe3(MCO)2 were fungicidal at MFC 33.33–66.67 μg/mL. Ultra-thin-layer TEM imaging suggested that SbMe3(MCO)2 targets the integrity of bacterial membranes. Overall, four of the studied G2 series compounds possess antimicrobial activity against a broad range of microbial pathogens, with particular potential against fungal pathogens, which will be explored in further studies.
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