RESUMEN
Antibiotic resistance is an ongoing problem in the treatment of bacterial diseases. Among the various antibacterial infections Staphylococcus aureus infections remain critical due to the increasing resistances, especially against the methicillin-resistant S. aureus (MRSA). We discovered novel antibacterial compounds with activities against both S. aureus and MRSA types. Structure-activity relationships (SAR) are discussed and show that the activity depends on the ring size of the anellated cycloalkane. Moreover, first substituent effects have been investigated for both the cycloalkane and the indole residues.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Cicloparafinas/química , Descubrimiento de Drogas , Indoles/química , Indoles/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/síntesis química , Relación Dosis-Respuesta a Droga , Indoles/síntesis química , Estructura Molecular , Relación Estructura-ActividadRESUMEN
Novel bisindolyl-cycloalkane indoles resulted from the reaction of aliphatic dialdehydes and indole. As bisindolyl-natural alkaloid compounds have recently been reported as inhibitors of the methicillin-resistant Staphylococcus aureus (MRSA)-pyruvate kinase (PK), we tested our novel compounds as MRSA PK inhibitors and now report first inhibiting activities. We discuss structure-activity relationships of structurally varied compounds. Activity influencing substituents have been characterized and relations to antibacterial activities of the most active compounds have been proved.