Synthesis and In vitro Evaluation of novel 5-nitroIndole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activities.

Synthesis and In vitro Evaluation of novel 5-nitroIndole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activities.
ChemMedChem. 2021 Jan 28;:
Authors: Nimbarte VD, Wirmer-Bartoschek J, Gande SL, Alshamleh I, Seibert M, Nasiri HR, Schnütgen F, Serve H, Schwalbe H
Abstract
Lead optimization strategies for compounds targeting c-Myc G quadruplex (G4) DNA are actively pursued to develop anticancer drugs. Here, we investigate the structure-activity-relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds i nteract with the terminal G-quartets (5' and 3' end) in a 2:1 stoichiometry.
PMID: 33508167 [PubMed - as supplied by publisher]

Source: ChemMedChem - January 28, 2021 Category: Chemistry Authors: Nimbarte VD, Wirmer-Bartoschek J, Gande SL, Alshamleh I, Seibert M, Nasiri HR, Schnütgen F, Serve H, Schwalbe H Tags: ChemMedChem Source Type: research