دورية أكاديمية
Rational Design of Antimalarial Drugs Using Molecular Modeling and Statistical Analysis.
| العنوان: | Rational Design of Antimalarial Drugs Using Molecular Modeling and Statistical Analysis. |
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| المؤلفون: | Santos CB; Laboratory of Modeling and Computational Chemistry, Federal University of Amapa, Macapa, Amapa, 68902-280, Brazil. breno@unifap.br., Lobato CC, Braga FS, Costa Jda S, Favacho HA, Carvalho JC, Macedo WJ, Brasil Ddo S, Silva CH, Silva Hage-Melim LI |
| المصدر: | Current pharmaceutical design [Curr Pharm Des] 2015; Vol. 21 (28), pp. 4112-27. |
| نوع المنشور: | Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Bentham Science Publishers Country of Publication: United Arab Emirates NLM ID: 9602487 Publication Model: Print Cited Medium: Internet ISSN: 1873-4286 (Electronic) Linking ISSN: 13816128 NLM ISO Abbreviation: Curr Pharm Des Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Saif Zone, Sharjah, U.A.E. : Bentham Science Publishers Original Publication: Schiphol, The Netherlands : Bentham Science Publishers, c1995- |
| مواضيع طبية MeSH: | Models, Molecular*, Antimalarials/*pharmacology , Artemisinins/*pharmacology , Plasmodium falciparum/*drug effects, Animals ; Antimalarials/chemistry ; Antimalarials/pharmacokinetics ; Artemisinins/chemistry ; Artemisinins/pharmacokinetics ; Caco-2 Cells ; Dogs ; Drug Design ; Humans ; Ligands ; Linear Models ; Madin Darby Canine Kidney Cells ; Models, Statistical ; Molecular Docking Simulation ; Quantitative Structure-Activity Relationship |
| مستخلص: | Artemisinin is an antimalarial compound isolated from Artemisia annua L. that is effective against Plasmodium falciparum. This paper proposes the development of new antimalarial derivatives of artemisinin from a SAR study and statistical analysis by multiple linear regression (MLR). The HF/6-31G** method was used to determine the molecular properties of artemisinin and 10 derivatives with antimalarial action. MEP maps and molecular docking were used to study the interface between ligand and receptor (heme). The Pearson correlation was used to choose the most important properties interrelated to the antimalarial activity: Hydration Energy (HE), Energy of the Complex (Ecplex), bond length (FeO1), and maximum index of R/Electronegativity of Sanderson (RTe+). After the Pearson correlation, 72 MLR models were built between antimalarial activity and molecular properties; the statistical quality of the models was evaluated by means of correlation coefficient (r), squared correlation coefficient (r(2)), explained variance (adjusted R(2)), standard error of estimate (SEE), and variance ratio (F), and only four models showed predictive ability. The selected models were used to predict the antimalarial activity of ten new artemisinin derivatives (test set) with unknown activity, and only eight of these compounds were predicted to be more potent than artemisinin, and were therefore subjected to theoretical studies of pharmacokinetic and toxicological properties. The test set showed satisfactory results for six new artemisinin compounds which is a promising factor for future synthesis and biological assays. |
| المشرفين على المادة: | 0 (Antimalarials) 0 (Artemisinins) 0 (Ligands) 9RMU91N5K2 (artemisinin) |
| تواريخ الأحداث: | Date Created: 20150529 Date Completed: 20160706 Latest Revision: 20210915 |
| رمز التحديث: | 20221213 |
| DOI: | 10.2174/1381612821666150528121423 |
| PMID: | 26017698 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1873-4286 |
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| DOI: | 10.2174/1381612821666150528121423 |