Elucidation of the Binding Mechanism of Coumarin Derivatives with Human Serum Albumin

Archit Garg, Darla Mark Manidhar, Mahesh Gokara, Chandramouli Malleda, Cirandur Suresh Reddy, S. Rajagopal

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Coumarin is a benzopyrone which is widely used as an anti-coagulant, anti-oxidant, anti-cancer and also to cure arthritis, herpes, asthma and inflammation. Here, we studied the binding of synthesized coumarin derivatives with human serum albumin (HSA) at physiological pH 7.2 by using fluorescence spectroscopy, circular dichroism spectroscopy, molecular docking and molecular dynamics simulation studies. By addition of coumarin derivatives to HSA the maximum fluorescence intensity was reduced due to quenching of intrinsic fluorescence upon binding of coumarin derivatives to HSA. The binding constant and free energy were found to be 1.957±0.01×105 M-1, -7.175 Kcal M-1 for coumarin derivative (CD) enamide; 0.837±0.01×105 M-1, -6.685 Kcal M-1 for coumarin derivative (CD) enoate, and 0.606±0.01×105 M-1, -6.49 Kcal M-1 for coumarin derivative methylprop (CDM) enamide. The CD spectroscopy showed that the protein secondary structure was partially unfolded upon binding of coumarin derivatives. Further, the molecular docking studies showed that coumarin derivatives were binding to HSA at sub-domain IB with the hydrophobic interactions and also with hydrogen bond interactions. Additionally, the molecular dynamics simulations studies contributed in understanding the stability of protein-drug complex system in the aqueous solution and the conformational changes in HSA upon binding of coumarin derivatives. This study will provide insights into designing of the new inspired coumarin derivatives as therapeutic agents against many life threatening diseases.

Original languageEnglish
Article numbere63805
JournalPLoS One
Volume8
Issue number5
DOIs
Publication statusPublished - May 28 2013

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Coumarins
coumarin
Serum Albumin
chemical derivatives
molecular dynamics
Molecular Dynamics Simulation
Molecular dynamics
Spectrum Analysis
human serum albumin
Fluorescence
fluorescence emission spectroscopy
Drug Stability
Circular dichroism spectroscopy
Secondary Protein Structure
fluorescence
circular dichroism spectroscopy
Coagulants
protein secondary structure
Protein Stability
coagulants

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Elucidation of the Binding Mechanism of Coumarin Derivatives with Human Serum Albumin. / Garg, Archit; Mark Manidhar, Darla; Gokara, Mahesh; Malleda, Chandramouli; Suresh Reddy, Cirandur; Rajagopal, S.

In: PLoS One, Vol. 8, No. 5, e63805, 28.05.2013.

Research output: Contribution to journalArticle

Garg, Archit ; Mark Manidhar, Darla ; Gokara, Mahesh ; Malleda, Chandramouli ; Suresh Reddy, Cirandur ; Rajagopal, S. / Elucidation of the Binding Mechanism of Coumarin Derivatives with Human Serum Albumin. In: PLoS One. 2013 ; Vol. 8, No. 5.
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