Density functional theory (DFT) and topological parameters based QSAR study of MK-886 analogues as bioactive mPGES-1 inhibitors

P. N. Tripathi*, Sunil Kumar S

Abstract

MK-886 derivatives are indole carboxylic acids. A series of MK-886 analogues showed selectivity and higher activity against the inducible mPGES-1 with the lowest IC50 value found being 3 nM. In this paper, DFT based quantum chemical and topological descriptors have been used for the development of QSAR models of MK-886 analogues. The descriptors that have been used are total energy, electron affinity, LogP, shape index (order 1), shape index (order 2), solvent accessibility surface area, valence connectivity index (order 1) and molar refractivity. Evaluation of descriptors has been done with the help of CAChe Pro software, using the DFT and PM3 Methods. The Project Leader program has been used for multi linear regression (MLR) analysis. Reliable QSAR models have been obtained from single descriptors namely total energy, LogP, shape index (order 2) and solvent accessibility surface area, therefore these descriptors appear important for the study of MK-886 analogues. It has been observed from our study that the best combination of descriptors is total energy, shape index (order 1), solvent accessibility surface area and valence connectivity index (order 1) for the QSAR study of MK-886 analogues and can be used to find out the activity of any new derivative of MK-886.