Journal of Molecular Modeling

, Volume 15, Issue 10, pp 1221–1228

Towards the design of Cyclooxygenase (COX) inhibitors based on 4′,5 di-substituted biphenyl acetic acid molecules: a QSAR study with a new DFT based descriptor - nucleus independent chemical shift

Original Paper

DOI: 10.1007/s00894-009-0481-6

Cite this article as:
Sarkar, A. & Mostafa, G. J Mol Model (2009) 15: 1221. doi:10.1007/s00894-009-0481-6


Cyclooxygenase (COX) is a well-known enzyme, which converts arachidonic acid to prostaglandins H2 (PGH2), which are the effective mediators of inflammation. 4′, 5 di-substituted 3-biphenyl acetic acids (BPA) and several α-methyl derivatives (MBPA) of it are widely used as powerful nonsteroidal anti-inflammatory and analgesic agents. We have chosen these activity data because the relation between the substituents and activity is not obvious and is hard to explain and also to show the superiority of DFT method. From the DFT results, various quantum chemical based descriptors were computed but the QSAR results showed that the descriptors based on frontier electron density and a new DFT based quantum chemical descriptor, nucleus independent chemical shift (NICS) are likely to be responsible for the in vitro inhibiting activity of BPA and MPBA. It has been proposed that NICS accounts for π…π interaction and indeed leads to a better result. To the best of our knowledge, this is the first use of NICS as a descriptor to get a better relationship to facilitate the design of COX inhibitors with potentially higher biological activity.


COX-inhibitionDFT-QSARFrontier electron densityNICSNSAIDπ…π interaction

Supplementary material

894_2009_481_MOESM1_ESM.doc (13 mb)
ESM 1(DOC 12.9 MB)

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of PhysicsAPC CollegeKolkata700131India
  2. 2.Department of PhysicsJadavpur UniversityKolakataIndia