2D and 3D QSAR studies of diarylpyrimidine HIV-1 reverse transcriptase inhibitors

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Rebehmed, J (Author) Other; Barbault, F (Author) Other; Catia Teixeira (Author) Other; Maurel, F (Author) Other

Journal

Title: Journal of Computer-Aided Molecular Design

Vol. 22

Pages: 831-841

ISSN: 0920-654X

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 10 Citations

Other information

Authenticus ID: P-008-TC1

DOI: 10.1007/s10822-008-9217-4

Abstract (EN): 2D and 3D QSAR studies were applied on a set of 28 diarylpyrimidine derivatives to model and understand their HIV-1 reverse transcriptase (RT) inhibitory activities. Special cares were taken to build our set of molecules according to their bioactive conformations which is crucial to elaborate good QSAR models. 2D QSAR was performed using the heuristic method in CODESSA which had led to a linear model (R(2) = 0.928 and s(2) = 0.015) between the inhibitory activity and five descriptors. CoMFA and CoMSIA models were established using SYBYL package of programs. The better predictive ability of the CoMSIA model (q(2) = 0.730) over the CoMFA model (q(2) = 0.597) was assigned to the large contribution of hydrogen-bonding interactions to the inhibitory activity. CoMSIA physicochemical properties are in agreement with the 2D QSAR descriptors. The CoMSIA PLS contour surfaces were mapped to the binding pocket of the RT and showed that the results obtained by the 2D and 3D models are in respect with the protein environment. This link permitted us to validate our model and give important insights for the structure activity interpretations. These results will guide further structural modification and prediction of new HIV-1 RT inhibitors.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11