In Vitro Activity and Atom Pair Fingerprint Analysis of Potent Hits from Malaria Box against Staphylococcus aureus Isolated from Cows with Clinical Mastitis

Staphylococcus aureus (S. aureus) is one of the most prevalent contagious bacterial pathogens causing clinical bovine mastitis. In the present study, plate (A), which consists of 80 compounds (40 drug-like and 40 probe-like), was assessed from the Malaria Box against the in vitro growth of S. aureus isolated from cows naturally infected with S. aureus. Anti-Staphylococcus aureus medications that are newer and more potent than those that have been used previously were discovered. Bioinformatics analysis for the potent identified hits was performed. Three compounds—two probe-like and one drug-like—showed strong inhibitory action against S. aureus growth in vitro. Among these hits, MMV665941 exhibited the highest minimum inhibitory concentration value of 0.0078. Combination therapy was carried out using the most potent anti-S. aureus medication, MMV665941, and the traditionally used anti-S. aureus drug, amoxicillin/clavulanate (Augmentin 625®). The atom pair fingerprint (APfp) analysis revealed that MMV665941 and Augmentin showed maximum structural similarity. Based on the results obtained, it can be concluded that the Medicines for Malaria Venture Box has a wealth of potential anti-S. aureus candidates.