Computer aided drug design of florfenicol to target chloramphenicol acetyltransferase of vibriosis causing pathogens

Vibriosis, a bacterial infection, is very much responsible for causing significant losses in the aquaculture industry. Chloramphenicol acetyltransferase is an antibiotic resistant enzyme present in the vibrio class of bacteria. Florfenicol, a benzene sulphonyl antibiotic is the lead molecule in this study. OSIRIS property explorer, Chemsketch, Molinspiration, pre ADMET tools were used for ligand modification, while AutoDock Vina, PyMOL, and LigPlot+ were used for protein–ligand docking analysis. Florfenicol demonstrated a free binding energy of −6.0 kcal/mol and poor ADMET properties. Ligand structures were optimized using “uff” forcefield and conjugate gradients algorithm. Primary drug designing was done with emphasis on ADMET properties that yielded a total of 15 modified ligands. Among these 15 ligands, F006 exhibited the highest dock score of −7.3 kcal/mol along with significant ADME properties and was hence chosen for further secondary modifications. Ligand F006 was further modified on the basis of ADMET properties to obtain 17 modified ligands. Among the 17 secondary ligands, F016 demonstrated strong binding affinity of −8.6 kcal/mol and also demonstrated significant ADME properties. Based on the results of this studies, the structure based computational drug design of florfenicol concluded that the modified ligand F016 designed in this study has good ADMET properties along with strong binding affinity towards the drug target chloramphenicol acetyltransferase protein and could be a potential solution in treating vibriosis.