Interactions of Porphyrin-Acridine Hybrids to DNA Duplexes and Quadruplex: In Silico Study

摘要

The binding modes of cationic porphyrin hybrids to DNA has been studied in a previous study. In the present research, cationic porphyrin-acridine hybrids bearing meso-substituted pyridine, imidazole, and pyrazole rings were investigated for their interaction with DNA. AutoDock Vina was used to dock 11 compounds to four different DNA duplexes, dodecamers d(CGCAAATTTGCG)2 (PDB code: 102D) and d(CGCGAATTCGCG)2 (PDB code: 1PRP), and hexamers d(CGATCG)2 (PDB code: 1Z3F) and d(TGATCA)2 (PDB code: 182D), as well as a human telomeric DNA quadruplex (PDB code: 1KF1). The binding mode and affinity of each compound were then compared to that of meso-tetrakis(4-methylpyridiniumyl)porphyrin (TMPyP). The hybrid compounds interacted with the DNA duplexes through intercalation and groove binding, while the interaction with DNA quadruplex was strictly stacking. Porphyrin-acridine hybrids with two meso-substituted diazolium rings exhibited higher affinity towards both DNA duplex and quadruplex than that of mono- and tri-substituted derivatives. Bis-H_2PyP-2AC resulted in the highest affinity towards DNAs representing minor groove binding, with binding free energies of –12.3 and –13.8 kcal/mol towards 102D and 1PRP, respectively, and bis-H_2ImP-2AC docked well with quadruplex DNA 1KF1 with a binding free energy of –11.6 kcal/mol.