Validation of Computational Methods Applied in Molecular Modeling of Artemisinin with Antimalarial Activity

Santos, Cleydson Breno Rodrigues dos; Vieira, Josinete Braga; Formigosa, Adriane da Silva; Costa, Elizabeth Viana Moraes da; Pinheiro, Mayara Tânia; Silva, Jocivânia Oliveira da; Macêdo, Williams Jorge de Cruz; Carvalho, José Carlos Tavares

doi:10.1166/jctn.2014.3394

Cited by 6 publications

(7 citation statements)

References 3 publications

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“…However, the minimum base 6-31G has several deficiencies; thus, a polarization function was included to improve upon this base (i.e., p orbitals represented by *). Thus, 6-31G* refers to basis set 6-31G with a polarization function for heavy atoms (i.e., atoms other than hydrogen), and 6-31G** refers to the inclusion of a polarization function for hydrogen and helium atoms [29][30][31][32][33][34][35].…”

Section: Determination Of the Theoretical Geometrical Parameters For mentioning

confidence: 99%

“…It then becomes necessary to include diffuse functions in the basis function associated with the configuration of a neutral metal atom to obtain a better description of the metal complex. The 6-31G** basis is particularly useful in the case of hydrogen bonds [30][31][32][33][34][35].…”

Section: Determination Of the Theoretical Geometrical Parameters For mentioning

confidence: 99%

“…Understanding the interactions between small molecules and their molecular targets should improve the ability to predict the toxic consequences that are responsible for the removal of many commercialized drugs and failures in the final stage drug development [35,[72][73][74].…”

Section: Pharmacokinetic and Toxicological Properties Of Test Compoundsmentioning

confidence: 99%

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A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

et al. 2014

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Abstract: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 OPEN ACCESSMolecules 2014, 19 10671 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 R 2 = ±0.0106, R 2 ajust = ±0.0125, s = ±0.0234, F (4,11) = ±12.7802, Q 2 = ±0.0088, SEV = ±0.0132, PRESS = ±0.4808 and S PRESS = ±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 (P CaCO2 ), cell permeability Maden Darby Canine Kidney (P MDCK ), skin permeability (P Skin ), plasma protein binding (PPB) and penetration of the blood-brain barrier (C Brain/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.

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Section: Determination Of the Theoretical Geometrical Parameters For mentioning

confidence: 99%

Section: Determination Of the Theoretical Geometrical Parameters For mentioning

confidence: 99%

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A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

et al. 2014

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“…This type of treatment shows that QSPR studies are important to obtain of molecular properties that take into account different aspects of chemical information, this information can be through experiments or theoretical calculations simple counting, consider the entire molecule, fragments or functional groups, knowledge of the 3D structure of the molecule or molecular graphics his or her simply formula, information defined by scalar values, vectors or scalar fields [109].…”

Section: Case Study On Aspirinmentioning

confidence: 99%

Application of Hartree-Fock Method for Modeling of Bioactive Molecules Using SAR and QSPR

Santos¹,

Lobato²,

Braga³

et al. 2014

CMB

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The central importance of quantum chemistry is to obtain solutions of the Schrödinger equation for the accurate determination of the properties of atomic and molecular systems that occurred from the calculation of wave functions accurate for many diatomic and polyatomic molecules, using Self Consistent Field method (SCF). The application of quantum chemical methods in the study and planning of bioactive compounds has become a common practice nowadays. From the point of view of planning it is important to note, when it comes to the use of molecular modeling, a collective term that refers to methods and theoretical modeling and computational techniques to mimic the behavior of molecules, not intend to reach a bioactive molecule simply through the use of computer programs. The choice of method for energy minimization depends on factors related to the size of the molecule, parameters of availability, stored data and computational resources. Molecular models generated by the computer are the result of mathematical equations that estimate the positions and properties of the electrons and nuclei, the calculations exploit experimentally, the characteristics of a structure, providing a new perspective on the molecule. In this work we show that studies of

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“…Recently, Santos et al [21] validated computational methods applied in the molecular modeling of artemisinin, proposing a combination of chemical quantum methods and statistical analysis to study the geometrical parameters of artemisinin in the region of the endoperoxide ring (1,2,13-trioxane). The PCA results indicated that their model was built with three main components (3 Cs), explaining 97.0861% of the total variance.…”

Section: Pca and Hca 31 Determination Of The Theoretical Geometricamentioning

confidence: 99%

Evaluation of Quantum Chemical Methods and Basis Sets Applied in the Molecular Modeling of Artemisinin

Santos¹,

Lobato²,

Vieira³

et al. 2013

CMB

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In this paper, we evaluate semiempirical methods (AM1, PM3, and ZINDO), HF and DFT (B3LYP) in different basis sets to determine which method best describes the sign and magnitude of the geometrical parameters of artemisinin in the region of the endoperoxide ring compared to crystallographic data. We also classify these methods using statistical analysis. The results of PCA were based on three main components, explaining 98.0539% of the total variance, for the geometrical parameters C3O13, O1O2C3, O13C12C12a, and O2C3O13C12. The DFT method (B3LYP) corresponded well with the experimental data in the hierarchical cluster analysis (HCA). The experimental and theoretical angles were analyzed by simple linear regression, and statistical parameters (correlation coefficients, significance, and predictability) were evaluated to determine the accuracy of the calculations. The statistical analysis exhibited a good correlation and high predictive power for the DFT (B3LYP) method in the 6-31G** basis set.

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Validation of Computational Methods Applied in Molecular Modeling of Artemisinin with Antimalarial Activity

Cited by 6 publications

References 3 publications

A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

A QSAR, Pharmacokinetic and Toxicological Study of New Artemisinin Compounds with Anticancer Activity

Application of Hartree-Fock Method for Modeling of Bioactive Molecules Using SAR and QSPR

Evaluation of Quantum Chemical Methods and Basis Sets Applied in the Molecular Modeling of Artemisinin

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