Design and Docking Studies of Novel Ciprofloxacin Derivatives as DNA Gyrase Inhibitors

Abstract

In this study, several flouro quinolones were examined, in order to design new effective antibacterial drugs (DNA gyrase inhibitors). Forty quinolone derivatives were designed using cheminformatics programmer (ACD/Lab); ACD/ChemSketch Freeware has been used to draw chemical structures, calculation of molecular properties (molecular weight, density, molar volume, polarizability and parachor), naming structures and prediction of log P. All flouroquinilones under study were sketched using SYBYL(sketch) and then converted into 3D structures and minimized using SYBYL-X 1.1and then inhibitors were saved in mol2 format and put in SYBYL databases ready for docking. -The structure ofDNA gyraseused was downloaded from protein data bank (PDB), and the receptor was prepared and minimized using SYBYL-X 1.1and saved using the pdb format. -Surflex-Dock protomol was generated, and the docking was performed .Docking results were analyzed by discovery studio software,which showed that the interaction between compound and residues in the binding site mainly were hydrogen bonds and π interactions. Among the ligands under investigation there are 34 ligands that show scores between (5.69-7.38) which are greater than ciprofloxacin (5.57) while the remained six compounds scores were less, the compound 1- cyclopropyl-6-fluoro-4-oxo-7-{[2-(phenylamino)ethyl]amino}-1,4-dihydroquinoline-3-carboxylic acid(ligand 10) was found to be the best ligand with highest fitness score in the docking (7.38).