| 1. |
- Ballante, Flavio, et al.
(author)
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Comprehensive model of wild-type and mutant HIV-1 reverse transciptases.
- 2012
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In: Journal of Computer-Aided Molecular Design. - : Springer Science+Business Media B.V.. - 0920-654X .- 1573-4951. ; 26:8, s. 907-19
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Journal article (peer-reviewed)abstract
- An enhanced version of COMBINE that uses both ligand-based and structure-based alignment of ligands has been used to build a comprehensive 3-D QSAR model of wild-type HIV-1 reverse transcriptase and drug-resistant mutants. The COMBINEr model focused on 7 different RT enzymes complexed with just two HIV-RT inhibitors, niverapine (NVP) and efavirenz (EFV); therefore, 14 inhibitor/enzyme complexes comprised the training set. An external test set of chiral 2-(alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones (DABOs) was used to test predictability. The COMBINEr model MC4, although developed using only two inhibitors, predicted the experimental activities of the test set with an acceptable average absolute error of prediction (0.89 pK (i)). Most notably, the model was able to correctly predict the right eudismic ratio for two R/S pairs of DABO derivatives. The enhanced COMBINEr approach was developed using only software freely available to academics.
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| 2. |
- Friggeri, Laura, et al.
(author)
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Pharmacophore assessment through 3-D QSAR : evaluation of the predictive ability on new derivatives by the application on a series of antitubercular agents.
- 2013
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In: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 53:6, s. 1463-74
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Journal article (peer-reviewed)abstract
- Pharmacophoric mapping is a useful procedure to frame, especially when crystallographic receptor structures are unavailable as in ligand-based studies, the hypothetical site of interaction. In this study, 71 pyrrole derivatives active against M. tuberculosis were used to derive through a recent new 3-D QSAR protocol, 3-D QSAutogrid/R, several predictive 3-D QSAR models on compounds aligned by a previously reported pharmacophoric application. A final multiprobe (MP) 3-D QSAR model was then obtained configuring itself as a tool to derive pharmacophoric quantitative models. To stress the applicability of the described models, an external test set of unrelated and newly synthesized series of R-4-amino-3-isoxazolidinone derivatives found to be active at micromolar level against M. tuberculosis was used, and the predicted bioactivities were in good agreement with the experimental values. The 3-D QSAutogrid/R procedure proved to be able to correlate by a single multi-informative scenario the different activity molecular profiles thus confirming its usefulness in the rational drug design approach.
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| 3. |
- Rotili, Dante, et al.
(author)
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2-(Alkyl/aryl)amino-6-benzylpyrimidin-4(3H)-ones as inhibitors of wild-type and mutant HIV-1 : enantioselectivity studies.
- 2012
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In: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:7, s. 3558-62
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Journal article (peer-reviewed)abstract
- The single enantiomers of two pyrimidine-based HIV-1 non-nucleoside reverse transcriptase inhibitors, 1 (MC1501) and 2 (MC2082), were tested in both cellular and enzyme assays. In general, the R forms were more potent than their S counterparts and racemates and (R)-2 was more efficient than (R)-1 and the reference compounds, with some exceptions. Interestingly, (R)-2 displayed a faster binding to K103N RT with respect to WT RT, while (R)-1 showed the opposite behavior.
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