CP-MLR derived QSAR rationales for the PPARy agonistic activity of the pyridyloxybenzene-acylsulfonamide derivatives

Raghuraj Parihar; Afsar Jahan; Brij Kishore Sharma

doi:10.30574/gscbps.2020.12.1.0231

Authors

Raghuraj Parihar Department of Chemistry, Government College, Bundi-323 001 (Rajasthan), India.
Afsar Jahan Department of Chemistry, Government College, Bundi-323 001 (Rajasthan), India.
Brij Kishore Sharma Department of Chemistry, Government College, Bundi-323 001 (Rajasthan), India.

DOI:

https://doi.org/10.30574/gscbps.2020.12.1.0231

Keywords:

QSAR, PPARg transactivation, combinatorial protocol in multiple linear regression (CP-MLR) analysis, Dragon descriptors, Pyridyloxybenzene-acylsulfonamides.

Abstract

QSAR rationales have been obtained for the PPARg transactivation activity of pyridyloxybenzene-acylsulfonamides in terms of 0D- to 2D-Dragon descriptors. The descriptors identified in CP-MLR analysis have highlighted the role of atomic mass, van der Waals volumes and polarizability through weighted 2D autocorrelations (GATS1v and GATS1p), modified Burden eigenvalue (BEHm4) and molecular weight (MW). Sum of topological distances between O and S atoms (descriptor T(O..S)), and N and Cl atoms (descriptor T(N..Cl)), average connectivity index chi-1(X1A) and Quadratic index (Qindex) have also shown dominance to optimize the PPARγ transactivation. Descriptors RBN and RBF suggested presence of rotatable bonds in a molecular structure for better PPARg activity. Applicability domain analysis revealed that the suggested model matches the high quality parameters with good fitting power and the capability of assessing external data and all of the compounds was within the applicability domain of the proposed model and were evaluated correctly.

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