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 (<b><i>G1</i></b>) 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 <b><i>G1</i></b> compounds with a trimethyl group, thereby generating a new series of compounds we refer to as "generation 2", <b><i>G2</i></b>. 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 (<i>Pseudomonas aeruginosa</i> PAO1, <i>Escherichia coli</i> S17 and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) NRS70) and two fungal (<i>Candida albicans</i> strain SC5314 and <i>Cryptococcus neoformans</i> 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 <i>C. albicans</i> and <i>C. neoformans</i> 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 <b><i>G2</i></b> 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.