biostudies-literatureCadoni EFundo Social Europeu e Programa Operacional Potencial HumanoFundação para a Ciência e a TecnologiaEuropean Structural & Investment FundsCOMPETE ProgramEuropean Structural & Investment Funds669https://www.ebi.ac.uk/biostudies/studies/S-EPMC8308870biostudies-literatureUnknown14(7)G-quadruplex (G4)-interactive small molecules have a wide range of potential applications, not only as drugs, but also as sensors of quadruplex structures. The purpose of this work is the synthesis of analogues of the bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure-activity relationships to apply to the design of other G4-interactive small molecules bearing bis-quinoline or bis-isoquinoline moieties. Thermal denaturation experiments revealed that non-methylated derivatives with a relative 1,4 position between the amide linker and the nitrogen of the quinoline ring are moderate G4 stabilizers, with a preference for the hybrid h-Telo G4, a 21-nt sequence present in human telomeres. Insertion of a positive charge upon methylation of quinoline/isPharmaceuticals (Basel, Switzerland)New (Iso)quinolinyl-pyridine-2,6-dicarboxamide G-Quadruplex Stabilizers. A Structure-Activity Relationship Study.PMC8308870SAICTPAC/0019/2015, UIDP/04138/2020 of iMed, UIDB/00709/2020 of CICS, PTDC/BIA-BFS/28419/2017, strategic project UIDB/04046/2020-UIDP/04046/2020 (BioISI)IF/00959/2015LISBOA-01-0145-FEDER-016405SAICTPAC/0019/2015Mendes EPaulo AVitor JCruz CCadoni EVictor BLCarvalho JEmidio RMMagalhaes PRfalseNew (Iso)quinolinyl-pyridine-2,6-dicarboxamide G-Quadruplex Stabilizers. A Structure-Activity Relationship Study.G-quadruplex (G4)-interactive small molecules have a wide range of potential applications, not only as drugs, but also as sensors of quadruplex structures. The purpose of this work is the synthesis of analogues of the bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure-activity relationships to apply to the design of other G4-interactive small molecules bearing bis-quinoline or bis-isoquinoline moieties. Thermal denaturation experiments revealed that non-methylated derivatives with a relative 1,4 position between the amide linker and the nitrogen of the quinoline ring are moderate G4 stabilizers, with a preference for the hybrid h-Telo G4, a 21-nt sequence present in human telomeres. Insertion of a positive charge upon methylation of quinoline/is2021-01-01T00:00:00Z2021 Jul2026-04-08T06:49:50.787Z2022-02-11T05:01:29.624ZS-EPMC83088703435809510.3390/ph14070669