Docking and 3D QSAR Studies on Substituted Cyclobutylphenyl Quinoline derivatives as inhibitors of bacterial DNA gyrase.

Docking and 3D QSAR studies were performed on Inhibitor of Bacterial DNA gyrase to develop a predictive Common Pharmacophore Hypothesis (CPH) and use it for alignment in PHASE; with a diverse set of 58 bacterial DNA gyrase inhibitors. A five point CPH with H-bond acceptor(A), Hydrophobic (H), Hydrogen bond Donor(D), Aromatic ring(R), a basic or positively ionizable feature. From them, the best pharmacophore hypothesis AAAPR gives a statistically significant and 3D QSAR model with 0.92 as R-squared value and 0.59 as Q-squared value. This hypothesis selected from a given set of data, so by correlating observed and estimated activity for the training set and a test set of molecules using partial least square analysis. Molecular interaction and binding affinities of these analogues, differing with nucleotides and amino acids are studied using molecular docking and MM-GB/SA method. Docking shows interaction with the Mutant and Wild receptor(2XCS) showing hydrogen bonding with unspecified residue deoxyribonucleotide (DC) and amino acid Ala1120 with hydroxyl group and carboxylate group forms a hydrogen bond with unspecified residue deoxyribonucleotide (DC) and Piperidine ring forms a positive charge DG and substituted phenyl ring shows pi-pi with DG. In Wild type docking interactions were decreased.