Interaction of indomethacin with calf thymus DNA: a multi-spectroscopic, thermodynamic and molecular modelling approach.
Mohammed Amir HusainHassan Mubarak IshqiTarique SarwarSayeed Ur RehmanMohammad TabishPublished in: MedChemComm (2017)
Indomethacin belongs to the acetic acid derivative class of non-steroidal anti-inflammatory drugs with diverse pharmacological and biological activities. Understanding the mechanism of interaction of drugs with possible target and off-target biomolecules can prove useful in the development of a rational drug designing system. In this paper, we have attempted to ascertain the mode of binding of indomethacin with calf thymus DNA (Ct-DNA) through various biophysical techniques and in silico molecular docking. Analysis of the UV-visible absorbance spectra and fluorescence emission profile of indomethacin upon addition of Ct-DNA indicates the formation of a drug-DNA complex. UV-visible absorbance and steady state fluorescence experiments revealed a binding constant on the order of 103 L mol-1, which is consistent with those of well-known groove binders. Competitive displacement studies with ethidium bromide, acridine orange and Hoechst 33258 further suggested that indomethacin binds to the minor groove of the Ct-DNA. The above observations were further confirmed by KI induced quenching experiments, DNA melting studies, CD spectral analysis and viscosity measurements. The thermodynamic parameters like spontaneous free energy (ΔG < 0) and large favourable enthalpy (ΔH < 0) obtained from isothermal calorimetry indicated the involvement of hydrogen bonding and van der Waals forces in the binding process. Molecular docking further corroborated the experimental results.
Keyphrases
- molecular docking
- single molecule
- circulating tumor
- cell free
- computed tomography
- molecular dynamics simulations
- anti inflammatory drugs
- nucleic acid
- dual energy
- high resolution
- magnetic resonance imaging
- oxidative stress
- contrast enhanced
- squamous cell carcinoma
- emergency department
- optical coherence tomography
- drug induced
- circulating tumor cells
- binding protein
- transcription factor
- molecular dynamics
- lymph node
- locally advanced
- quantum dots