RESUMEN
Aim: Antibiotic resistance is an alarming issue, as multidrug-resistant bacteria are growing worldwide, hence the decrease of therapeutic potential of available antibiotic arsenal. Among these bacteria, Staphylococcus aureus was pointed by the WHO in the pathogens list to be prioritized in drug development. Methods: We report the use of chemical similarity models for the virtual screening of new antibacterial with structural similarity to known inhibitors of FabI. The potential inhibitors were experimentally evaluated for antibacterial activity and membrane disrupting capabilities. Results & conclusion: These models led to the finding of four new compounds with antibacterial activity, one of which having antimicrobial activity already reported in the literature.
Asunto(s)
Antibacterianos/farmacología , Enoil-ACP Reductasa (NADH)/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/química , Evaluación Preclínica de Medicamentos , Enoil-ACP Reductasa (NADH)/metabolismo , Inhibidores Enzimáticos/química , Humanos , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Staphylococcus aureus/metabolismoRESUMEN
Oxidized collagen, wherein lysine residues are converted to the aldehyde allysine, is a universal feature of fibrogenesis, i.e. actively progressive fibrosis. Here we report the small molecule, allysine-binding positron emission tomography probe, 68Ga-NODAGA-indole, that can noninvasively detect and quantify pulmonary fibrogenesis. We demonstrate that the uptake of 68Ga-NODAGA-indole in actively fibrotic lungs is 7-fold higher than in control groups and that uptake is linearly correlated ( R2 = 0.98) with the concentration of lung allysine.