Macrocyclization of bis-indole quinolines for selective stabilization of G-quadruplex DNA structures.

ABSTRACT: The recognition of G-quadruplex (G4) DNA structures as important regulatory elements in biological mechanisms, and the connection between G4s and the evolvement of different diseases, has sparked interest in developing small organic molecules targeting G4s. However, such compounds often lack drug-like properties and selectivity. Here, we describe the design and synthesis of a novel class of macrocyclic bis-indole quinolines based on their non-macrocyclic lead compounds. The effects of the macrocyclization on the ability to interact with G4 DNA structures were investigated using biophysical assays and molecular dynamic simulations. Overall, this revealed compounds with potent abilities to interact with and stabilize G4 structures and a clear selectivity for both G4 DNA over dsDNA and for pa

SUBMITTER: Das RN 

PROVIDER: S-EPMC8162405 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature