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

Abstract

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 × 10⁶ for BRDR1, 0.37 × 10⁶ for BRDR2, 1.72 × 10⁶ for BRDR3 and 3.20 × 10⁶ 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

Keywords:

• Berberine derivative
• deoxyribonucleic acid
• isothermal titration calorimetry

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work is financially supported by Department of Science & Technology and Biotechnology, Government of West Bengal, India, sanction No. 1852(Sanc.)/ST/P/S&T/15G-3/2019. We gratefully acknowledge the Chemistry Department and USIC, Vidyasagar University for their instrumental facilities from DST-FIST and UGC-SAP programs.