Minor Groove DNA Binders as Antimicrobial Agents. 1. Pyrrole Tetraamides Are Potent Antibacterials against Vancomycin Resistant Enteroccoci and Methicillin Resistant Staphylococcus aureus

摘要: A new series of short pyrrole tetraamides are described whose submicromolar DNA binding affinity is an essential component for their strong antibacterial activity. This class compounds related to the linked bis-netropsins and bis-distamycins, but here, only one amino-pyrrole-carboxamide unit amidine tail connected either side a central dicarboxylic acid linker. The highest degree binding, measured by compound-induced changes in UV melting temperatures AT-rich oligomer, was observed flat, aromatic linkers with no inherent bent, i.e., terephthalic or 1,4-pyridine-dicarboxylic acid. However, activity critically size N-alkyl substiutent unit. None commonly used methyl-pyrrole showed Isoamyl- cyclopropylmethylene-substituted dipyrrole derivatives have minimum inhibitory concentrations range. In vitro toxicity against human T-cells studied all compounds. which inhibited cell growth neither directly correlated nor seemed depend strongly on nature substituents.