Abstract

Infection occurring in the skin and its associated soft tissues such as loose connective tissue and mucous membranes is known as “Acute Bacterial Skin and Skin Structure Infection (ABSSSI)”. Till 2008, ABSSSI is recognized as complicated skin and skin structure infection (cSSSI) and uncomplicated skin and skin structure infection (uSSSI). Delafloxacin (DLX), a fluoroquinolone antibiotic which is used to treat ABSSSI. In this study, we have seized Canonical SMILES of DLX from PubChem Compound Database of National Center for Biotechnology Information and predicted the targets using the method of “Shaping the interactive landscape of bioactive molecules” and retrieved 4EKK, 5T31, 2O5K, 3M1S, 4MQS and 4MQT protein crystal structures. The energy minimization of DLX was performed by Universal Force Field (UFF) using the steepest descent algorithm with 2000 iteration to obtain the optimized structures. To obtain the best binding energy there was used Autodock Vina docking protocol. The main structure of DLX was modified with -CF3, -OCH3, -OCH2CH3, -OCH2CF3 and -Br groups. The DLX-CF3 modified DLX showed binding energy -11.4 kcal/mol with protein 4MQT of muscarinic acetylcholine receptor M2 family compared to the main drug showed binding energy -9.7 kcal/mol with the same protein. All the modified drugs showed considerable Homo-Lumo, thermodynamic properties and pharmacokinetics properties. DLX containing trifluoromethane derivative will be the best inhibitor against muscarinic acetylcholine receptor M2 induced skin infection. Keywords: ABSSSIs, Delafloxacin, Molecular modeling, Virtual screening, 4MQT