Spectroscopic and viscometric determination of DNA-binding modes of some bioactive dibenzodioxins and phenazines

Apeksha Ashok Phadte,Subhadeep Banerjee,Nayan Anand Mate,Arnab Banerjee

doi:10.1016/j.bbrep.2019.100629

Apeksha Ashok Phadte, Subhadeep Banerjee + Show 2 more

Open Access

https://doi.org/10.1016/j.bbrep.2019.100629

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Abstract

Push-pull dibenzodioxins and phenazines having ‘anthracene-like’ planar structures and good charge transfer character had been previously synthesised in our laboratory. The dibenzodioxins had earlier proven their anti-proliferative nature against HeLa tumor cell lines. Since phenazines are structural analogues of the former, these molecules were evaluated in course of the current study for their cytotoxic action against HeLa cell lines and they exhibited strong anti-tumor activity. This behavior could be related to their good DNA binding property. The DNA binding modes of molecules 1–4 (Fig. 1) were evaluated using various experimental techniques and they interacted with DNA in a non-covalently by both intercalative as well as groove binding mechanisms. Molecule 1 follows predominantly intercalative binding mode whereas molecules 2 and 3 have nearly equal and opposite preferences for both groove binding and intercalative modes. For molecule 4, groove binding is preferred mode of binding to DNA. A rationale for such differential binding behaviour is provided based on the subtle structural differences in our synthesised dibenzodioxins and phenazines. Elucidation of the mode of a molecule-DNA-binding event is relevant for understanding the mechanism of action of these molecules and will help promote further research into designing better DNA targeting small molecules.

Highlights

Planar ‘anthracene-like’ molecules exhibit strong anti-tumor activity arising from their good DNA binding property [1a-b]
We have focused our research on design and synthesis of push-pull dibenzodioxins and phenazines as attractive options due to their planar ‘anthracene-like’ structures and well established bioactivity [3,4]
Since our synthesised phenazines have structural similarity with dibenzodioxins, we evaluated the anti-proliferative action of compounds 3 & 4 against human cervical cancer HeLa cell line

Summary

Introduction

Planar ‘anthracene-like’ molecules exhibit strong anti-tumor activity arising from their good DNA binding property [1a-b]. Structural analogues of PAHs could be used as platforms for designing small molecular drugs. We have focused our research on design and synthesis of push-pull dibenzodioxins and phenazines as attractive options due to their planar ‘anthracene-like’ structures and well established bioactivity [3,4]. We previously synthesised push-pull dibenzodioxin molecules (Fig. 1), and they exhibited promising in vitro cytotoxicity against HeLa tumor cell line and no cytotoxicity against normal HEK 293 and HaCaT cell lines [5,6]. Phenazines have structural resemblance with dibenzodioxins, we are interested in exploring their in vitro cytotoxicity against suitable tumor cell lines

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Conclusion