Synthesis of some new arylazo-coumarin derivatives and their comparative biological activity studies: Cytotoxicity, gene expression, DNA binding, BSA binding, and in silico analysis

Abstract

The four azo coumarin derivatives (1–4) have been synthesized using a diazo coupling reaction where compounds (2) and (3) are newly synthesized and fully characterized by different spectroscopic methods. A comparative biological study has been carried out with the synthesized compounds to find the effect of the chloro group at the benzene ring at different positions in azo coumarin derivatives. The theoretical calculations reveal that the order of the biological activity is 4 > 2 > 3 > 1. The cytotoxicity evaluation using human brain glioblastoma cancer cell lines, LN-229 shows that the order of effectiveness of compounds is 4 > 2 > 3 > 1 which confirmed the theoretical predictions but compound (1) increases cell viability of N9 microglial cells of mice potentially. The gene expression study shows all the synthesized compounds have anti-inflammatory activity by upregulating SOCS3. The interaction of the synthesized compounds (1–4) with CT-DNA and BSA has been investigated using UV–vis absorption, fluorescence displacement, and isothermal titration calorimetric (ITC) methods. All the compounds bind with CT-DNA through a minor groove binding manner and with BSA but compound (4) binds strongly with CT-DNA and BSA. The thermodynamic parameters ΔH°, ΔG°, and TΔS° are calculated and the ITC data shows the binding process is energetically feasible. In silico analysis supports all the experimental outcomes regarding DNA and BSA binding.