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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2013-12-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/1/367 |
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| author | Cleydson Breno R. Santos Josinete B. Vieira Cleison C. Lobato Lorane I. S. Hage-Melim Raimundo N. P. Souto Clarissa S. Lima Elizabeth V. M. Costa Davi S. B. Brasil Williams Jorge C. Macêdo José Carlos T. Carvalho |
| author_facet | Cleydson Breno R. Santos Josinete B. Vieira Cleison C. Lobato Lorane I. S. Hage-Melim Raimundo N. P. Souto Clarissa S. Lima Elizabeth V. M. Costa Davi S. B. Brasil Williams Jorge C. Macêdo José Carlos T. Carvalho |
| author_sort | Cleydson Breno R. Santos |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T03:03:27Z |
| format | Article |
| id | doaj.art-206ee2da914b4435a91fe94a02d83357 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T03:03:27Z |
| publishDate | 2013-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-206ee2da914b4435a91fe94a02d833572022-12-22T00:40:34ZengMDPI AGMolecules1420-30492013-12-0119136739910.3390/molecules19010367molecules19010367A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial ActivityCleydson Breno R. Santos0Josinete B. Vieira1Cleison C. Lobato2Lorane I. S. Hage-Melim3Raimundo N. P. Souto4Clarissa S. Lima5Elizabeth V. M. Costa6Davi S. B. Brasil7Williams Jorge C. Macêdo8José Carlos T. Carvalho9Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, BrazilPostgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Macapá 68902-280, Amapá, Amazon, BrazilLaboratory of Drug Research, School of Pharmaceutical Sciences, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, BrazilLaboratory of Drug Research, School of Pharmaceutical Sciences, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, BrazilInstitute of Technology, Federal University of Pará, Av. Augusto Corrêa, 01, Belém 66075-900, Pará, Amazon, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Macapá 68902-280, Amapá, Amazon, BrazilPostgraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Macapá 68902-280, Amapá, Amazon, BrazilThe 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.http://www.mdpi.com/1420-3049/19/1/367artemisininantimalarial activityHF/6-31G**molecular dockingMEPsSARQSAR |
| spellingShingle | Cleydson Breno R. Santos Josinete B. Vieira Cleison C. Lobato Lorane I. S. Hage-Melim Raimundo N. P. Souto Clarissa S. Lima Elizabeth V. M. Costa Davi S. B. Brasil Williams Jorge C. Macêdo José Carlos T. Carvalho A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity Molecules artemisinin antimalarial activity HF/6-31G** molecular docking MEPs SAR QSAR |
| 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 | artemisinin antimalarial activity HF/6-31G** molecular docking MEPs SAR QSAR |
| url | http://www.mdpi.com/1420-3049/19/1/367 |
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