The interaction analysis for CID44610309, CID44259709, CID13964550 and quercetin is shown in Table 1. The docking simulation revealed the top docking poses were found to be docked at the binding cavity showing both bonded and non-bonded interaction. The top ten docking hits showed common interaction with Trp294
and Glu299. The snapshots of ligand–protein interaction, electrostatic interaction and the binding mode for the top docking hit CID44610309 is shown in Fig. 2. The ADME of the docking hits ranged between 0.036 and 0.28 for solubility, 3.36 × 104–7.92 × 104 for absorption and 0.59–1.12 for distribution. The LogD at various pH ranges from 1.51 to 2.81, 1.5 to 2.82, 1.43 to 2.81, 1.07 to 2.76 and 0.48 to 2.64 for stomach, duodenum, jejunum, ileum, blood and colon respectively. The percentage human oral bioavailability for the compounds ranged from 30% to 70%. Interestingly, CID44610309, selleck chemical CID44258703 and CID11834044 showed no or lesser health effects compared to the other docked compounds (Fig. 3). These three compounds could be lead molecule or a potential anti-cancer compound. The three-dimensional structure of iNOS of G. gallus was generated using Modeller 9v8. The structure assessment of the generated
model revealed the model is reliable and a quality model with stable energies. Additionally the molecular docking studies with quercetin and its analogues into the binding Forskolin mouse cavity of
iNOS showed the analogues having more favourable interaction than quercetin with favourable rerank score, docking score and hydrogen bonding energy. As quercetin is known for having anti-cancer property, the analogues docked aminophylline at the binding cavity could also possess anti-cancer property as it is 95% similar to quercetin. Interestingly, among the docked compounds the ADME–toxicity prediction revealed CID44610309, CID44258703 and CID11834044 have lesser health effects and LD50 as compared to the other docked compounds. Hence we conclude that these compounds could be a potential lead molecule and supports for experimental testing. All authors have none to declare. JPR solutions funded our article to publish. “
“Bacterial infections are leading cause of death for millions of people. This is because of the emergence of new disease agents and the development of resistant strains. Moreover, the pathogens have evolved effective approaches to counteract the biocidal action of antibiotics. Even though many antibiotics have been developed, very few antibiotics have proved effective against bacterial resistant strains. Therefore, it is extremely important to design and develop new approaches that overcome these limitations. The persistence of antibiotic resistant bacteria has renewed interest in the use of silver and silver based compounds including silver nanoparticles.