Insight into Stabilization of G-Quadruplex in c-MYC Region with Phenanthroimidazoisoindol-Acrylates and their Binding Behaviour towards Human Serum Albumin

Abstract

The interaction of G-quadruplex (non-canonical DNA) with suitable compounds for their stabilization at the promoter region of oncogenes has become a potential anticancer approach. We have studied the interaction of phenanthroimidazoisoindol-acrylates derivatives with c-MYC G-quadruplex. A series of 20 compounds were evaluated for their anticancer activity against human cancer cell lines, where compounds 3 fa, 3 ha, and 3 ae have shown the broad-spectrum anticancer activities against most of the cancer cell lines and inactive towards normal cell lines. Various spectroscopic techniques have been used to study the interaction of these compounds. The studies reveal the strong binding of all three compounds with c-MYC G-quadruplex with significant selectivity over dsDNA, with binding constant of the order of 10⁶ M^-1. All three compounds bind effectively with HSA, which is a carrier protein, with binding constant of the order of 10⁵ M^-1. These results show that phenanthroimidazoisoindol-acrylate derivatives exhibit specificity towards G4 DNA, highlighting their potential as effective anticancer agents targeting the c-MYC G-quadruplex.

Keywords: G-quadruplex; Human Serum Albumin; anticancer; phenanthroimidazoisoindol-acrylate.