13, 14, 15 and 16 In the present study the binding interactions of some of the 3,4-heteroannelated quinolin-2-ones with DNA Gyrase as well as their antibacterial activity has been reported. These compounds are assumed to bind to inhibit the DNA Gyrase 2 of S. aureus in a similar fashion as ciprofloxacin does, since the compounds share structural similarity with Ciprofloxacin. The potential compounds are identified and their antibacterial activity is evaluated against S. aureus and Escherichia coli and
reported here. To study the MK-1775 research buy extent of interaction of the synthesized 3,4-heteroannelated quinolin-2-ones with the DNA Gyrase of S. aureus, the compounds were docked to the protein using the GOLD 3.2 (Genetic Optimization for inhibitors ligand Docking) software. The docked poses of each ligand were analyzed and fitness Scores are calculated with Silver. Screening of antibacterial activity of title compounds was done by adopting disc diffusion method as described by Cruickshank et al (1975)17 using S. aureus
Gram +ve (Oxford strain) and E. coli Gram −ve (NCTC 10148). The synthesized compounds were constructed and prepared for docking using the Ligprep Protocol of Maestro. Ligand minimization was done using OPLS 2005 Force field. The synthesized compounds were constructed and prepared for docking using the Ligprep Protocol of Maestro. A high resolution (2.1 Å) crystal structure of S. aureus DNA Gyrase is selected and docked using GOLD 3.2. The GOLD find more fitness function is made up of four components: protein–ligand hydrogen bond energy, protein–ligand Vander Waals energy, ligand internal vdw energy and ligand torsional strain energy and the fitness score is taken as the negative of the sum of the component energy terms. The docked poses of each ligand were visualized and the interactions were analyzed with Silver. The best Fitness
Scores for each ligand are tabulated along with the details of H-bonds and other interactions in Table 1. The binding poses of the ligands to the proteins are shown in Fig. 1. Compound 1b has the highest fitness score of 51.23. Compounds 1a, 1c, 2d and 2j also showed good fitness scores Suplatast tosilate next to 1b. 11 compounds show good fitness score values as compared to Ciprofloxacin. Screening of antibacterial activity of title compounds was done by adopting disc diffusion method as described by Cruickshank et al (1975).17 The compounds were dissolved in appropriate solvents (AR grade) and Whatman No.1 filter paper discs of 6 mm diameter were prepared with various concentrations of test compounds ranging from 200 to 3.125 μg/disc. The test organisms used were S. aureus Gram +ve (Oxford strain) and E. coli Gram −ve (NCTC 10148).