Analysis of substituted 8-hydroxyquinolines as potential antibacterial agents in silico and their antibacterial activity

The collection of forty-nine 8-hydroxyquinoline derivatives, primarily substituted at C5, but also at C6 or C7, was designed and studied by computational methods using Molinspiration, SwissADME, Osiris and AntiBac-Pred tools. In silico calculations are essential tools in modern chemoinformatics, often published in professional literature as well as in the field of research of new antibacterial active compounds, developed to replace existing antibiotics that fail due to increased resistance of bacteria. Nitroxoline™ and the group of 8-hydroxyquinoline derivatives with their broad antibacterial effects and potential for extensive derivatization of the skeleton show promising direction in the development of new antibacterial active substances. Twenty 8-hydroxyquinoline derivatives were also evaluated on their antibacterial activity against eight selected G + and G − bacterial strains with a defined resistance mechanism. All structures met Lipinski's criteria, twenty-one structures were interesting from the point of view of individual or average value of the bioactivity prediction score and fourteen structures showed one or more mechanisms of toxicity prediction. Additionally, eleven structures showed low GI absorption rates or the inability to cross the BBB barrier, fourteen substances showed a BRENK or PAIN warnings, eleven were undesirable substrates of P-glycoprotein, and all structures predicted the same level of bioavailability and a relatively low rates of liver metabolism. Virtual structures 17 , 25 , 35 and 43 can be favored for the continuity of next study. The bioactivity scores obtained suggest the potential of studied structures in designing and development of new active antibacterial agents. Atomic charges were calculated using the HypherChem program package and all data were analyzed using statistical method of Principal Component Analysis (PCA).