Intercalation, Cytotoxicity, and Molecular Modeling of Acenaphtho[1,2-b]pyrrole Chromophores as a New Family of Antitumor Agents

To explore new platform for DNA intercalation and potent antitumor agent, a series of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters chromophores has been studied. Their intercalation geometries with DNA were revealed through absorption titration, SYBR Green-DNA melt curve, circular dichroism(CD), and docking studies. It was identified that some of the compounds could intercalate into DNA along their long axis parallel to the base-pair long axis, making right-handed B form DNA transform to A-like conformation. Their binding potency varied with the different steric hindrance. Their cytotoxicity(IC₅₀) against MCF-7 cells was found to range between 1.3 to 40.9 μmol/L by MTT assay. Interestingly, the IC₅₀ values did not show any obvious correlation to their binding constants with DNA. The chromophore with a carboxyl group exhibited the most potency of intercalating DNA and could be the promising precursor for the future intercalator for DNA, while the bromide demonstrated the highest cytotoxic activity in this series of compounds.