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

Abstract

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.

The Multifaceted Opportunities Provided by the Pheomelanin-Inspired 1,4-Benzothiazine Chromophore: A Still-Undervalued Issue

“…These include mainly antihypertensive, antipsychotic, antidiabetic, anticancer, anti-inflammatory, antimalarial, antiviral, antimicrobial, antitubercular, and analgesic activities. Most of these properties, which are generally associated with the ability to inhibit specific enzymes, have been found to be strictly related to the unique nitrogen and sulfur relative arrangement in the benzothiazine scaffold [1][2][3][4][5][6]. Some papers have also reported the use of 1,4-benzothiazines as dyestuffs, color photographic developers, corrosion inhibitors, and antioxidants for rubbers and elastomers [1].…”