QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents
Malaria is a disease caused by protozoan parasites of the genus Plasmodium that affects millions of people worldwide. In recent years there have been parasite resistances to several drugs, including the first-line antimalarial treatment. With the aim of proposing new drugs candidates for the treatme...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-09-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/9/2348 |
| _version_ | 1819261608391606272 |
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| author | Letícia Santos-Garcia Marco Antônio de Mecenas Filho Kamil Musilek Kamil Kuca Teodorico Castro Ramalho Elaine Fontes Ferreira da Cunha |
| author_facet | Letícia Santos-Garcia Marco Antônio de Mecenas Filho Kamil Musilek Kamil Kuca Teodorico Castro Ramalho Elaine Fontes Ferreira da Cunha |
| author_sort | Letícia Santos-Garcia |
| collection | DOAJ |
| description | Malaria is a disease caused by protozoan parasites of the genus Plasmodium that affects millions of people worldwide. In recent years there have been parasite resistances to several drugs, including the first-line antimalarial treatment. With the aim of proposing new drugs candidates for the treatment of disease, Quantitative Structure–Activity Relationship (QSAR) methodology was applied to 83 N-myristoyltransferase inhibitors, synthesized by Leatherbarrow et al. The QSAR models were developed using 63 compounds, the training set, and externally validated using 20 compounds, the test set. Ten different alignments for the two test sets were tested and the models were generated by the technique that combines genetic algorithms and partial least squares. The best model shows r2 = 0.757, q2adjusted = 0.634, R2pred = 0.746, R2m = 0.716, ∆R2m = 0.133, R2p = 0.609, and R2r = 0.110. This work suggested a good correlation with the experimental results and allows the design of new potent N-myristoyltransferase inhibitors. |
| first_indexed | 2024-12-23T19:44:30Z |
| format | Article |
| id | doaj.art-bbdc80730984419c88303e473cefbe4b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T19:44:30Z |
| publishDate | 2018-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-bbdc80730984419c88303e473cefbe4b2022-12-21T17:33:35ZengMDPI AGMolecules1420-30492018-09-01239234810.3390/molecules23092348molecules23092348QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial AgentsLetícia Santos-Garcia0Marco Antônio de Mecenas Filho1Kamil Musilek2Kamil Kuca3Teodorico Castro Ramalho4Elaine Fontes Ferreira da Cunha5Departamento de Química, Universidade Federal de Lavras, Lavras 37200-000, BrazilDepartamento de Química, Universidade Federal de Lavras, Lavras 37200-000, BrazilDepartment of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50005, Czech RepublicDepartment of Chemistry, Faculty of Science, University of Hradec Kralove, Hradec Kralove 50005, Czech RepublicDepartamento de Química, Universidade Federal de Lavras, Lavras 37200-000, BrazilDepartamento de Química, Universidade Federal de Lavras, Lavras 37200-000, BrazilMalaria is a disease caused by protozoan parasites of the genus Plasmodium that affects millions of people worldwide. In recent years there have been parasite resistances to several drugs, including the first-line antimalarial treatment. With the aim of proposing new drugs candidates for the treatment of disease, Quantitative Structure–Activity Relationship (QSAR) methodology was applied to 83 N-myristoyltransferase inhibitors, synthesized by Leatherbarrow et al. The QSAR models were developed using 63 compounds, the training set, and externally validated using 20 compounds, the test set. Ten different alignments for the two test sets were tested and the models were generated by the technique that combines genetic algorithms and partial least squares. The best model shows r2 = 0.757, q2adjusted = 0.634, R2pred = 0.746, R2m = 0.716, ∆R2m = 0.133, R2p = 0.609, and R2r = 0.110. This work suggested a good correlation with the experimental results and allows the design of new potent N-myristoyltransferase inhibitors.http://www.mdpi.com/1420-3049/23/9/2348malariaN-myristoyltransferasedrug developmentQSARmosquito-borne protozoal infection |
| spellingShingle | Letícia Santos-Garcia Marco Antônio de Mecenas Filho Kamil Musilek Kamil Kuca Teodorico Castro Ramalho Elaine Fontes Ferreira da Cunha QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents Molecules malaria N-myristoyltransferase drug development QSAR mosquito-borne protozoal infection |
| title | QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents |
| title_full | QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents |
| title_fullStr | QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents |
| title_full_unstemmed | QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents |
| title_short | QSAR Study of N-Myristoyltransferase Inhibitors of Antimalarial Agents |
| title_sort | qsar study of n myristoyltransferase inhibitors of antimalarial agents |
| topic | malaria N-myristoyltransferase drug development QSAR mosquito-borne protozoal infection |
| url | http://www.mdpi.com/1420-3049/23/9/2348 |
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