Synthesis of novel calix[4]arene p-benzazole derivatives and investigation of their DNA binding and cleavage activities with molecular docking and experimental studies

Abstract

In this study, novel p-benzimidazole-derived calix[4]arene compounds with different structures, and a benzothiazole-derived calix[4]arene compound, were synthesized by a microwave-assisted method and their structures were determined by FTIR, 1H NMR, 13C NMR, MALDI-TOF mass spectroscopy, and elemental analysis. The effects of functional calixarenes against bacterial (pBR322 plasmid DNA) and eukaryotic DNA (calf thymus DNA = CT-DNA) were investigated. The studies with plasmid DNA have shown that compounds 6 and 10 containing methyl and benzyl groups, respectively, have DNA cleavage activity at the highest concentrations (10 000 μM). Interactions with plasmid DNA using some restriction enzymes (BamHI and HindIII) were also investigated. The binding ability of p-substituted calix[4]arene compounds towards CT-DNA was examined using UV-vis and fluorescence spectroscopy and it was determined that some compounds showed efficiency. In particular, it was observed that the functional compounds (10 and 5) containing benzyl and chloro-groups had higher activity (Kb binding constants were found to be 7.1 × 103 M−1 and 9.3 × 102 M−1 respectively) on DNA than other compounds. Competitive binding experiments using ethidium bromide also gave an idea about the binding properties. Docking studies of the synthesized compounds with DNA were performed to predict the binding modes, affinities and noncovalent interactions stabilizing the DNA–compound complexes at the molecular level. Docking results were in good agreement with the experimental findings on the DNA binding activities of compounds. Based on these results, this preliminary study could shed light on future experimental antibacterial and/or anticancer research.