biostudies-literatureAndreasson MKnut och Alice Wallenbergs StiftelseKempestiftelsernaVetenskapsr?det2202-2219https://www.ebi.ac.uk/biostudies/studies/S-EPMC10860144biostudies-literatureUnknown67(3)G-Quadruplex (G4) DNA structures are important regulatory elements in central biological processes. Small molecules that selectively bind and stabilize G4 structures have therapeutic potential, and there are currently >1000 known G4 ligands. Despite this, only two G4 ligands ever made it to clinical trials. In this work, we synthesized several heterocyclic G4 ligands and studied their interactions with G4s (e.g., G4s from the <i>c-MYC</i>, <i>c-KIT</i>, and <i>BCL-2</i> promoters) using biochemical assays. We further studied the effect of selected compounds on cell viability, the effect on the number of G4s in cells, and their pharmacokinetic properties. This identified potent G4 ligands with suitable properties and further revealed that the dispersion component in arene-arene interactionsJournal of medicinal chemistryExploring the Dispersion and Electrostatic Components in Arene-Arene Interactions between Ligands and G4 DNA to Develop G4-Ligands.PMC10860144SMK21-0059VR-NT 2021-04805JCK-3159 SMK-16322019.0307VR-MH 2018-0278VR-NT 2017-05235Wanrooij SAndreasson MDoimo MChorell EDonzel MBerner AOverman JPemberton NAbrahamsson AChao YKQuiroga AEriksson AfalseExploring the Dispersion and Electrostatic Components in Arene-Arene Interactions between Ligands and G4 DNA to Develop G4-Ligands.G-Quadruplex (G4) DNA structures are important regulatory elements in central biological processes. Small molecules that selectively bind and stabilize G4 structures have therapeutic potential, and there are currently >1000 known G4 ligands. Despite this, only two G4 ligands ever made it to clinical trials. In this work, we synthesized several heterocyclic G4 ligands and studied their interactions with G4s (e.g., G4s from the <i>c-MYC</i>, <i>c-KIT</i>, and <i>BCL-2</i> promoters) using biochemical assays. We further studied the effect of selected compounds on cell viability, the effect on the number of G4s in cells, and their pharmacokinetic properties. This identified potent G4 ligands with suitable properties and further revealed that the dispersion component in arene-arene interactions2024-01-01T00:00:00Z2024 Feb2025-04-04T12:06:10.604Z2025-04-04T12:06:10.604ZS-EPMC108601443824160910.1021/acs.jmedchem.3c02127