Aminoalkoxyfluorenones and aminoalkoxybiphenyls: DNA binding modes.

ABSTRACT

Many evidences suggest that DNA-drug interaction in the minor groove and the intercalation of drugs into DNA may play critical roles in antiviral, antimicrobial, and antitumor activities. As a continuous effort to develop novel antiviral agents, the series of planar fluorenone (3a-7d) were synthesized and used along with nonplanar biphenyls (11a-d) for the comparative analysis of their interaction with DNA. The chemical structure of new compounds was confirmed by 1H NMR, 13C NMR and mass spectra as well as elemental analysis. DNA affinity of 3a-7d and 11a-d was evaluated by ethidium bromide displacement assay. Affinity constant (lgKa) of 3a-7d was found to be approximately two orders of magnitude higher than constants of corresponding 11a-d. The molecular docking of aminoalkoxybiphenyls (11a-d) into minor grove of five different nucleotide sequences (d(CCIICICCII), d(CGCGTTAACGCG), d(CGCGATATCGCG), d(GGCCAATTGG), d(GGATATATCC)) demonstrated their binding capacity to the specific DNA site. The linear least squares fitting technique was successfully applied to derive an equation describing the relationship between lgKa and SF.