Abstract:
Antibiotic resistance has emerged as a global health emergency, necessitating the need for the development of novel drugs. This study evaluated antibacterial activity of pyrazolyl sulfonamide compounds and their palladium complexes. All compounds were coded. Broth microdilution method was utilized to determine minimum inhibitory and bactericidal concentrations (MIC and MBC). Whereas the compounds demonstrated antibacterial activity against Staphylococcus aureus, Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus epidermidis, and Corynebacterium striatum, no activity was observed against Staphylococcus cohnii and Enterococcus faecalis. Compound CA11B, a derivative of N, N-tetramethyl sulfonamide, demonstrated the strongest antibacterial activity against S. aureus, S. hominis, and S.haemolyticus (MIC = 0.5 – 8 μg/mL). Although most of the test compounds were active against at least two organisms, the sulfamoyl-phenyl derivatives (CA45A/B), dichloro-palladium (CA50A/B/D), and dimethyl-phenyl sulfonamides (CA-032) derivatives were narrow spectrum in activity. When CA11B was combined with the positive control antibiotic (tetracycline), an antagonistic effect was observed in S. haemolyticus and S. hominis. Interestingly, all other compounds were synergistic with tetracycline when combined in the tested organism, except CA50B and CA45A, which were indifferent and antagonistic, respectively. The time-kill assays performed on synergistic combinations showed that CA45B, CA-O32, CA47, CO-3, CA48A at concentrations ≥ MIC, achieved 3 log10 CFU/mL colony reduction of S. haemolyticus. Similar trend was observed for CA50A, and CA50D in S. hominis. The time-kill kinetics results in this study showed the potent inhibitory and bactericidal activity of the tested compounds. In conclusion, the compounds showed promising potency against the different resistant strains tested. It is recommended that these compounds be further assessed for their toxicological effects and tested against a diverse array of bacteria to further ascertain their efficacy.
