| Full text | |
| Author(s): |
Kronenberger, Thales
[1, 2]
;
Windshugel, Bjorn
[2]
;
Wrenger, Carsten
[1]
;
Honorio, Kathia M.
[3, 4]
;
Maltarollo, Vinicius G.
[5]
Total Authors: 5
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Unit Drug Discovery, Sao Paulo - Brazil
[2] Fraunhofer Inst Mol Biol & Appl Ecol IME, Hamburg - Germany
[3] Univ Sao Paulo, Sch Arts Sci & Humanities, Sao Paulo - Brazil
[4] ABC Fed Univ, Ctr Nat Sci & Humanities, Santo Andre, SP - Brazil
[5] Univ Fed Minas Gerais, Fac Pharm, Dept Pharmaceut Prod, Belo Horizonte, MG - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS; v. 36, n. 16, p. 4378-4391, DEC 10 2018. |
| Web of Science Citations: | 2 |
| Abstract | |
Farnesoid X receptor (FXR) is a nuclear receptor related to lipid and glucose homeostasis and is considered an important molecular target to treatment of metabolic diseases as diabetes, dyslipidemia, and liver cancer. Nowadays, there are several FXR agonists reported in the literature and some of it in clinical trials for liver disorders. Herein, a compound series was employed to generate QSAR models to better understand the structural basis for FXR activation by anthranilic acid derivatives (AADs). Furthermore, here we evaluate the inclusion of the standard deviation (SD) of EC50 values in QSAR models quality. Comparison between the use of experimental variance plus average values in model construction with the standard method of model generation that considers only the average values was performed. 2D and 3D QSAR models based on the AAD data set including SD values showed similar molecular interpretation maps and quality (Q(LOO)(2), Q((F2))(2), and Q((F3))(2)), when compared to models based only on average values. SD-based models revealed more accurate predictions for the set of test compounds, with lower mean absolute error indices as well as more residuals near zero. Additionally, the visual interpretation of different QSAR approaches agrees with experimental data, highlighting key elements for understanding the biological activity of AADs. The approach using standard deviation values may offer new possibilities for generating more accurate QSAR models based on available experimental data. (AU) | |
| FAPESP's process: | 14/03644-9 - Targeting alternative ligand-binding sites in nuclear receptors using computational and experimental screening |
| Grantee: | Thales Kronenberger |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 14/27313-1 - Targeting alternative ligand-binding sites in nuclear receptors using computational and experimental screening |
| Grantee: | Thales Kronenberger |
| Support Opportunities: | Scholarships abroad - Research Internship - Doctorate |