Discovery & Evaluation of novel fluorescence molecules for selective recognition of G-quadruplexes structure

AbstractCurrently, G-quadruplex structure targeting strategies are considered as a promising anticancer approach. In the search of selective and potent G-quadruplex binders, Here we discuss an analysis of a few chroman derivatives ligands: (A) chroman 7-[2-pyrrolo]-pyrrole-[1,2-a]12H pyrrolino[2,3-b]chroman-4-one, and (C) 4-methyl-7-[2-pyrrolo]-pyrrole[1,2-a]12H pyrrolino[2,3-b]chroman-4-one and their respective borondifluoride complexes B and D as a quadruplex targeting compounds which found to stabilize G-quadruplex structure. To investigate the binding characteristics of these molecules with G-quadruplex vs. duplex selectivity,In vitrobiophysical studies were performed by steady-state fluorescence, UV-visible titration, fluorescent TO displacement assay, CD thermal melting, circular dichroism spectroscopy, and cellular imaging by employing both telomeric and PRCC G-quadruplex forming sequences. Our investigation shows that these chromam ligands and their complexes are able to selectively bind and stabilize parallel and mixed hybrid topology of G-quadruplex bothIn vitroand in cellular conditions. A molecular docking study also suggests the binding of these compounds with G-quadruplex conformation. Collectively our study suggests these chroman complexes as a potentially useful fluorescent chemical product for G-quadruplex specific ligands and expands an option for G-quadruplex targeting ligands.