Evaluation of the size effect of hydrophobic ring substitution on 9-O position of berberine on DNA binding

The interaction of deoxyribonucleic acid (DNA) with medicinally significant small molecules has long piqued the interest of researchers because its applications are directly related to the discovery of new classes of drugs. Keeping this in mind, here we report berberine derivatives and their interaction with calf thymus DNA (CT-DNA). In this report we discussed on the structural perspectives and thermodynamic characteristics of the interaction of four 9-O-substituted berberines (BRDR1 to BRDR4) with CT-DNA. The binding affinity of BRDR-DNA complexes increased with increasing the cycloalkane ring size of the substitution except BRDR2. The binding constant value obtained from UV-Visible spectral analysis was 1.12 x 10(6) for BRDR1, 0.37 x 10(6) for BRDR2, 1.72 x 10(6) for BRDR3 and 3.20 x 10(6) for BRDR4. Ferrocyanide quenching experiments revealed unequivocally that the analogues except BRDR2 had a partly intercalative binding to DNA. From the ITC experiment it was found that the bindings of BRDR1, BRDR3 and BRDR4 to DNA was favoured by negative enthalpy and positive entropy while BRDR2 was driven by positive enthalpy and positive entropy. In all cases the hydrophobic interaction plays a crucial role. Thus, the complete multispectroscopic and thermodynamic binding studies may be useful for new drug design and development.Communicated by Ramaswamy H. Sarma

Automated summary

This report discusses the structural and thermodynamic characteristics of the interaction between four 9-O-substituted berberines and CT-DNA. The analogues, except BRDR2, showed partly intercalative binding to DNA. Hydrophobic interaction plays a crucial role in this process. The complete multispectroscopic and thermodynamic binding studies are useful for drug design and development.