A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity
The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-07-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/8/10670 |
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| author | Josinete B. Vieira Francinaldo S. Braga Cleison C. Lobato César F. Santos Josivan S. Costa José Adolfo H. M. Bittencourt Davi S. B. Brasil Jocivânia O. Silva Lorane I. S. Hage-Melim Williams Jorge C. Macêdo José Carlos T. Carvalho Cleydson Breno R. Santos |
| author_facet | Josinete B. Vieira Francinaldo S. Braga Cleison C. Lobato César F. Santos Josivan S. Costa José Adolfo H. M. Bittencourt Davi S. B. Brasil Jocivânia O. Silva Lorane I. S. Hage-Melim Williams Jorge C. Macêdo José Carlos T. Carvalho Cleydson Breno R. Santos |
| author_sort | Josinete B. Vieira |
| collection | DOAJ |
| description | The Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11) = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (PSkin), plasma protein binding (PPB) and penetration of the blood-brain barrier (CBrain/Blood), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers. |
| first_indexed | 2024-04-13T10:53:19Z |
| format | Article |
| id | doaj.art-56cb1f4946d04c30bc6b25ee8d73dc51 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T10:53:19Z |
| publishDate | 2014-07-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-56cb1f4946d04c30bc6b25ee8d73dc512022-12-22T02:49:36ZengMDPI AGMolecules1420-30492014-07-01198106701069710.3390/molecules190810670molecules190810670A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer ActivityJosinete B. Vieira0Francinaldo S. Braga1Cleison C. Lobato2César F. Santos3Josivan S. Costa4José Adolfo H. M. Bittencourt5Davi S. B. Brasil6Jocivânia O. Silva7Lorane I. S. Hage-Melim8Williams Jorge C. Macêdo9José Carlos T. Carvalho10Cleydson Breno R. Santos11Laboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilLaboratory of Drug Research, School of Pharmaceutical Sciences, Federal University of Amapá, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilPostgraduate Program in Pharmaceutical Sciences, Federal University of Amapá, Rod JK Km 2, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilPostgraduate Program in Pharmaceutical Sciences, Federal University of Amapá, Rod JK Km 2, Macapá, Amapá 68902-280, BrazilLaboratory of Modeling and Computational Chemistry, Federal University of Amapá, Rod JK Km2, Macapá, Amapá 68902-280, BrazilThe Density Functional Theory (DFT) method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with different degrees of cytotoxicity against the human hepatocellular carcinoma HepG2 line. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) were employed to select the most important descriptors related to anticancer activity. The significant molecular descriptors related to the compounds with anticancer activity were the ALOGPS_log, Mor29m, IC5 and GAP energy. The Pearson correlation between activity and most important descriptors were used for the regression partial least squares (PLS) and principal component regression (PCR) models built. The regression PLS and PCR were very close, with variation between PLS and PCR of R2 = ±0.0106, R2ajust = ±0.0125, s = ±0.0234, F(4,11) = ±12.7802, Q2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and SPRESS = ±0.0057. These models were used to predict the anticancer activity of eight new artemisinin compounds (test set) with unknown activity, and for these new compounds were predicted pharmacokinetic properties: human intestinal absorption (HIA), cellular permeability (PCaCO2), cell permeability Maden Darby Canine Kidney (PMDCK), skin permeability (PSkin), plasma protein binding (PPB) and penetration of the blood-brain barrier (CBrain/Blood), and toxicological: mutagenicity and carcinogenicity. The test set showed for two new artemisinin compounds satisfactory results for anticancer activity and pharmacokinetic and toxicological properties. Consequently, further studies need be done to evaluate the different proposals as well as their actions, toxicity, and potential use for treatment of cancers.http://www.mdpi.com/1420-3049/19/8/10670artemisininanticancer activitymolecular modelingB3LYP/6-31G**QSAR |
| spellingShingle | Josinete B. Vieira Francinaldo S. Braga Cleison C. Lobato César F. Santos Josivan S. Costa José Adolfo H. M. Bittencourt Davi S. B. Brasil Jocivânia O. Silva Lorane I. S. Hage-Melim Williams Jorge C. Macêdo José Carlos T. Carvalho Cleydson Breno R. Santos A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity Molecules artemisinin anticancer activity molecular modeling B3LYP/6-31G** QSAR |
| title | A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity |
| title_full | A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity |
| title_fullStr | A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity |
| title_full_unstemmed | A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity |
| title_short | A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity |
| title_sort | qsar pharmacokinetic and toxicological study of new artemisinin compounds with anticancer activity |
| topic | artemisinin anticancer activity molecular modeling B3LYP/6-31G** QSAR |
| url | http://www.mdpi.com/1420-3049/19/8/10670 |
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