The Benzothiazine Core as a Novel Motif for DNA-Binding Small Molecules

A new series of 4H-1,3-benzothiazine dyes were prepared and fully characterized in an aqueous medium. Benzothiazine salts were synthesized either through the classical synthetic pathway using Buchwald-Hartwig amination or through economical and environmentally friendly electrochemical synthesis. The latest synthetic approach employs successful electrochemical intramolecular dehydrogenative cyclization of N-benzylbenzenecarbothioamides to form 4H-1,3-benzothiazines. 4H-1,3-Benzothiazines were evaluated as novel DNA/RNA probes. Through the use of several methods such as UV/vis spectrophotometric titrations, circular dichroism and thermal melting experiments, the binding of four benzothiazine-based molecules to polynucleotides was examined. Compounds 1 and 2 acted as DNA/RNA groove binders, thus suggesting the potential of these compounds as novel DNA/RNA probes. This is a proof-of-concept study and will be expanded to include SAR/QSAR studies.

Automated summary

A new series of 4H-1,3-benzothiazine dyes were synthesized and characterized. Two synthetic pathways, Buchwald-Hartwig amination and electrochemical synthesis, were used to prepare benzothiazine salts. Electrochemical intramolecular dehydrogenative cyclization was employed to form 4H-1,3-benzothiazines. The binding of these compounds to polynucleotides was examined, and compounds 1 and 2 showed potential as DNA/RNA groove binders.