Design, synthesis, DNA binding studies and evaluation of anticancer potential of novel substituted biscarbazole derivatives against human glioma U87 MG cell line.

Abstract

In this research paper, we report the design and synthesis of novel substituted biscarbazole derivatives which were characterized by 1H and 13C NMR, high resolution mass spectroscopy (HRMS). The SAR study of the compounds is reported based on different substituents and their positions in the biscarbazole scaffold. In vitro cytotoxicity of the compounds was evaluated against human glioma U87 MG cell line by MTT assay for 24h. The IC50 values of the compounds (30-35, 48-53 and 54-62) were calculated at the concentration range from 1.00µM to 500µM. The compound 34 showed the most significant in vitro cytotoxicity (IC50=3.9µM) against human glioma U87 MG cell line and was found to be better than standard drugs used for the treatment of brain tumors such as temozolomide (IC50=100µM) and carmustine (IC50=18.2µM) respectively. To determine the mode of binding of compound 34 with CT-DNA, various biophysical techniques like UV-spectrophotometer, fluorescence, circular dichroism, viscosity, topoisomerase assay and molecular docking analysis, were used. Our results demonstrated groove binding mode of interaction of the compound 34 with CT-DNA with a plausible static bio-molecular quenching rate constant (Kq) 1.7×1012 M-1s-1. The studies of biscarbazole derivatives are anticipated to develop potential novel anticancer agents against brain tumors.