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A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity
The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs) and molecular docking were used to investigate the interaction between ligands and the...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271440/ https://www.ncbi.nlm.nih.gov/pubmed/24381053 http://dx.doi.org/10.3390/molecules19010367 |
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author | Santos, Cleydson Breno R. Vieira, Josinete B. Lobato, Cleison C. Hage-Melim, Lorane I. S. Souto, Raimundo N. P. Lima, Clarissa S. Costa, Elizabeth V. M. Brasil, Davi S. B. Macêdo, Williams Jorge C. Carvalho, José Carlos T. |
author_facet | Santos, Cleydson Breno R. Vieira, Josinete B. Lobato, Cleison C. Hage-Melim, Lorane I. S. Souto, Raimundo N. P. Lima, Clarissa S. Costa, Elizabeth V. M. Brasil, Davi S. B. Macêdo, Williams Jorge C. Carvalho, José Carlos T. |
author_sort | Santos, Cleydson Breno R. |
collection | PubMed |
description | The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs) and molecular docking were used to investigate the interaction between ligands and the receptor (heme). Principal component analysis and hierarchical cluster analysis were employed to select the most important descriptors related to activity. The correlation between biological activity and molecular properties was obtained using the partial least squares and principal component regression methods. The regression PLS and PCR models built in this study were also used to predict the antimalarial activity of 30 new artemisinin compounds with unknown activity. The models obtained showed not only statistical significance but also predictive ability. The significant molecular descriptors related to the compounds with antimalarial activity were the hydration energy (HE), the charge on the O11 oxygen atom (QO11), the torsion angle O1-O2-Fe-N2 (D2) and the maximum rate of R/Sanderson Electronegativity (RTe(+)). These variables led to a physical and structural explanation of the molecular properties that should be selected for when designing new ligands to be used as antimalarial agents. |
format | Online Article Text |
id | pubmed-6271440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62714402018-12-20 A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity Santos, Cleydson Breno R. Vieira, Josinete B. Lobato, Cleison C. Hage-Melim, Lorane I. S. Souto, Raimundo N. P. Lima, Clarissa S. Costa, Elizabeth V. M. Brasil, Davi S. B. Macêdo, Williams Jorge C. Carvalho, José Carlos T. Molecules Article The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs) and molecular docking were used to investigate the interaction between ligands and the receptor (heme). Principal component analysis and hierarchical cluster analysis were employed to select the most important descriptors related to activity. The correlation between biological activity and molecular properties was obtained using the partial least squares and principal component regression methods. The regression PLS and PCR models built in this study were also used to predict the antimalarial activity of 30 new artemisinin compounds with unknown activity. The models obtained showed not only statistical significance but also predictive ability. The significant molecular descriptors related to the compounds with antimalarial activity were the hydration energy (HE), the charge on the O11 oxygen atom (QO11), the torsion angle O1-O2-Fe-N2 (D2) and the maximum rate of R/Sanderson Electronegativity (RTe(+)). These variables led to a physical and structural explanation of the molecular properties that should be selected for when designing new ligands to be used as antimalarial agents. MDPI 2013-12-30 /pmc/articles/PMC6271440/ /pubmed/24381053 http://dx.doi.org/10.3390/molecules19010367 Text en © 2013 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Santos, Cleydson Breno R. Vieira, Josinete B. Lobato, Cleison C. Hage-Melim, Lorane I. S. Souto, Raimundo N. P. Lima, Clarissa S. Costa, Elizabeth V. M. Brasil, Davi S. B. Macêdo, Williams Jorge C. Carvalho, José Carlos T. A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity |
title | A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity |
title_full | A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity |
title_fullStr | A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity |
title_full_unstemmed | A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity |
title_short | A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity |
title_sort | sar and qsar study of new artemisinin compounds with antimalarial activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271440/ https://www.ncbi.nlm.nih.gov/pubmed/24381053 http://dx.doi.org/10.3390/molecules19010367 |
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