Evaluation
of diflunisal a difluoro-derivative of salicylic acid as an inhibitor of
human serum albumin using molecular docking tools
A.D.
Stephen1*, S.M. Shankar2, R.N. Devi3, S.
Maruthamuthu2, A.M. Musthafa4, M. Pannipara5
and A.G. Al-Sehemi5
1Department of
Physics, PSG College of Arts and Science, Coimbatore-641 014, India
2Department of
Physics, PSG Institute of Technology and Applied Research, Coimbatore-641
062, India
3Department of
Physics, Fatima college, Madurai-625 001, India
4Department of
General Studies (Physics Group), Jubail University College (Male Branch),
Royal Commission of Jubail, 31961, Kingdom of Saudi Arabia
5Research Center
for Advanced Materials Science, King Khalid University, Abha, 62529, Saudi
Arabia
*Corresponding
Author Email : stevepearlin@gmail.com
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Abstract
Aim:
To evaluate the binding interaction of diflunisal at active site of Human
Serum Albumin (HSA), an important enzyme responsible for osteoarthritis
disease.
Methodology: The gas phase molecule was optimized with
B3LYP/6-311G** basis set, while a single point energy calculation was carried
out for the molecule lifted from the active site. Bader’s theory of atoms in
molecules (AIM) was used to determine the electron density and Laplacian of
electron density. The protein was assigned with polar hydrogens and Kollman
charges. Iterated local search procedure was performed during docking, during
this, both protein and ligand were considered as rigid. Among the ten poses,
lowest binding energy pose was considered for further ligand protein
interaction analysis and QTAIM studies.
Results:
A close observation of the results shows that diflunisal has interactions in
the binding sites IIA and IIIA of HSA as reported earlier. Two strong
classical H-bonding interactions, three hydrophobic contacts with the amino
acids VAL456, ALA194 andARG197, two close fluorine interactions, and two
Pi-Sigma interactions have been observed. Apart from the H-bond interactions,
the stability of HAS-Diflunisal complex was further empathized by five
hyrdrophobic interactions framed between hydroxyl benzoic acid ring with
ALA194, GLN459 and ARG197amino acid residue and difluorobenzene ring with
ALA194 and VAL456.
Interpretation: The results of drug-likeness study
showed that diflunisal is highly reactive and less toxic.
Key words: Binding affinity, Diflunisal, Human Serum Albumin,
Inflammation, Molecular docking, Pain
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