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metadata.artigo.dc.title: 3D-QSAR CoMFA/CoMSIA models based on theoretical active conformers of HOE/BAY-793 analogs derived from HIV-1 protease inhibitor complexes
metadata.artigo.dc.creator: Cunha, Elaine Fontes Ferreira da
Sippl, Wolfgang
Ramalho, Teodoricode Castro
Antunes, Octavio Augusto Ceva
Alencastro, Ricardo Bicca de
Albuquerque, Magaly Girão
metadata.artigo.dc.subject: 3D-QSAR
CoMFA/CoMSIAHIV-1 protease inhibitor HOE/BAY-793
PeptidomimeticC2-Symmetric diol
Molecular modeling
metadata.artigo.dc.publisher: Elsevier Nov-2009
metadata.artigo.dc.identifier.citation: CUNHA, E. F. F. da et al. 3D-QSAR CoMFA/CoMSIA models based on theoretical active conformers of HOE/BAY-793 analogs derived from HIV-1 protease inhibitor complexes. European Journal of Medicinal Chemistry, [S.l.], v. 44, n. 11, p. 4344-4352, Nov. 2009. DOI: 10.1016/j.ejmech.2009.05.016.
metadata.artigo.dc.description.abstract: The three-dimensional quantitative structure–activity relationships (3D-QSAR) of a series of HOE/BAY-793 analogs (C2-symmetric diol peptidomimetics), developed by Budt and co-workers [Bioorg. Med. Chem. 3 (1995) 559] as inhibitors of HIV-1 protease (HIV-PR), were studied using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Theoretical active conformers for these peptidomimetics were generated, derived from modeled protease inhibitor complexes, in order to orient the compounds superposition and to afford a consistent alignment. The best CoMFA model (N = 27, q2 = 0.637, R2 = 0.991) showed contributions of the steric (45.7%) and electrostatic (54.3%) fields to the activity, while the best CoMSIA model (N = 27, q2 = 0.511, R2 = 0.987) showed contributions of the electrostatic (68.5%) and hydrogen bond donor (37.5%) fields. The models were also external validated using four compounds (test set) not included in the model generation process. The statistical parameters from both models indicate that the data are well fitted and have high predictive ability. Moreover, the resulting 3D CoMFA/CoMSIA contour maps provide useful guidance for designing highly active ligands. The CoMFA/CoMSIA models were also compared with previous 4D-QSAR models [E.F.F. da Cunha, M.G. Albuquerque, O.A.C. Antunes, R.B. de Alencastro, QSAR Comb. Sci. 24 (2005), 240–253.].
metadata.artigo.dc.language: en_US
Appears in Collections:DQI - Artigos publicados em periódicos

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