Synthesis, Characterization and Antimicrobial Activity of Trimethylantimony(V) Biscyanoximates, a New Family of Antimicrobials.

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 () 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 compounds with a trimethyl group, thereby generating a new series of compounds we refer to as "generation 2", . 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 SbMeL 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 ( PAO1, S17 and methicillin-resistant (MRSA) NRS70) and two fungal ( strain SC5314 and strain H99) pathogens. Two compounds, SbMe(MCO) and SbMe(2,4-diClPhCO), were active against bacterial strains and inhibited the growth of PAO1 and MRSA with MICs of 50 and 100 µg/mL, respectively. Three compounds, SbMe(MCO), SbMe(ECO) and SbMe(TCO), were active against fungal strains and inhibited either one of or both and at MICs of 2.6-66.67 μg/mL. In addition, SbMe(TCO) and SbMe(MCO) were fungicidal at MFC 33.33-66.67 μg/mL. Ultra-thin-layer TEM imaging suggested that SbMe(MCO) targets the integrity of bacterial membranes. Overall, four of the studied 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.