Gold(III) porphyrins: Synthesis and interaction with G-quadruplex DNA

G-quadruplex nucleic acids (G4s) are RNA and DNA secondary structures involved in the regulation of multiple key biological processes. They can be found in telomeres, oncogene promoters, RNAs, but also in viral genomes. Due to their unique structural features, very distinct from the canonical duplexes or single-strands, G4s represent promising pharmacological targets for small molecules, namely G4-ligands. Gold(III) penta-cationic porphyrins, as specific G4 ligands, are able to inhibit HIV-1 infectivity and their antiviral activity correlates with their affinity for G4s. Up to now, one of the best antiviral compounds is meso-5,10,15,20-tetrakis[4-(N-methyl-pyridinium-2-yl)phenyl]porphyrinato gold(III) (1). Starting from this compound, we report a structure/affinity relationship study of gold(III) cationic porphyrins to find out the best porphyrin candidate for functionalization, in order to study the antiviral mechanism of action of these gold(III) porphyrins.

Automated summary

G-quadruplex nucleic acids (G4s) are RNA and DNA secondary structures that regulate key biological processes and are potential targets for small molecule drugs. Gold(III) penta-cationic porphyrins, specific G4 ligands, can inhibit HIV-1 infectivity by interacting with G4s. A study on the structure/affinity relationship of gold(III) cationic porphyrins aims to identify the best candidate for functionalization and investigate the antiviral mechanism of action.