Iodinated curcumin as a novel anti-bacterial agent to combat Methicillin-resistant Staphylococcus aureus in bovine mastitis: In silico analysis, synthesis and in vitro evaluation

Background: Methicillin-resistant Staphylococcus aureus (MRSA) contagion is raising serious concern to the dairy cattle. One successful approach to treat MRSA infection is that the potential drug candidate should excite the allosteric view of active site, and form a stable interaction with the penicillin binding proteins (PBP2a), tyrosyl t-RNA synthetase (TyrRs) and thymidylate kinase (TMK) causing cell lysis and bacterial cell death. Objectives: Hence, the aim of current study is the identification of a promising active drug molecule which can serve as a ligand for successful inhibition of S. aureus bacterial protein. Methods: 1,7-bis(4-hydroxy-3-methoxy phenoxy)-1,2,6,7- tetraiodoheptane-3,5-dione is an iodinated curcumin, which displayed a stable hydrophobic interaction (docking score~ -8.45 kcal/mol) with the allosteric binding site of PBP2a as compared to ‘curcumin’ (-7.10 kcal/mol) in addition to S. aureus TyrRs and TMK protein. Results: Moreover, the results were cross validated with Hex8.0 program. Molecular simulations studies were also conducted using SwissDock molecular docking program and Autodock Tools-1.5.6. The RMSD plot produced from the simulation study depicted minimum deviation per residue of protein and the deviation was found to be in the range of 0.12 to 1.02Å. Iodinated curcumin demonstrated Minimum Inhibitory Concentration (MIC) values at 60 and 80-µg/ml remarkably lower (P<0.05) than the MIC values (150 and 220-µg/ml) of curcumin against bacterial strains S. aureus and MRSA, respectively, as measured by cup-plate method. However, MIC values of the standard drug, linezolid were remarkably higher than 2.5 and 7.5-µg/ml against S. aureus and MRSA, respectively. Conclusion: In conclusion, iodinated curcumin warrants further in vivo anti-bacterial analysis as a potential treatment regimen against resistant MRSA strains in dairy cattle mastitis.