Chemico-biological interaction of Etravirine and its β-Cyclodextrin complex with macromolecular targets

Abstract

The interaction of etravirine with β-cyclodextrin is analyzed by UV–visible absorption, infrared, fluorescence, nuclear magnetic resonance, two-dimensional rotational frame nuclear Overhauser effect spectroscopy, and molecular modeling studies. The 4-hydroxy-3, 5-dimethylbenzonitrile moiety is found to take part in the binding. The stoichiometry of the inclusion complex of ET with β-CD is 1:1 with the binding constant of 2.03 × 10³ mol⁻¹ dm³. The binding of ET with calf thymus DNA (ctDNA) and bovine serum albumin (BSA) protein is investigated in the presence and the absence of β-CD. Fluorescence enhancement is observed during the binding of ET with ctDNA in the absence of β-CD, whereas in the presence of β-CD, fluorescence quenching is observed. The binding constants of the binding of ET and ET–β-CD to ctDNA are 7.84 × 10⁴ and 4.38 × 10⁴ mol⁻¹ dm³, respectively. The binding constant of the binding of ET and ET–β-CD to BSA are 3.14 × 10⁴ and 1.6396 × 10⁴ mol⁻¹ dm³, respectively. The apparent binding constants between ET–β-CD complex and ctDNA or BSA protein decreases significantly. The numbers of binding sites of interaction of ET with BSA protein and the binding distance between BSA protein and ET the absence and the presence of β-CD differ. β-CD modulates the binding of ET with the macromolecular targets.

Graphical abstract

β-Cyclodextrin act as carrier of etravirine for the binding with DNA and Protein targets.

Keywords:

• Etravirine
• β-Cyclodextrin
• Calf thymus DNA
• Bovine serum albumin
• Host–guest complex