Interaction between artemisinin and heme. A Density Functional Theory study of structures and interaction energies

Araújo, Jocley Queiroz; Carneiro, José Walkimar de M.; Araújo, M. T. de; Leite, Franco Henrique Andrade; Taranto, Alex Gutterres

doi:10.1016/j.bmc.2008.03.033

Cited by 30 publications

(25 citation statements)

References 32 publications

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“…The molecules are distributed into two regions separately in PC1. The left side contains samples with the lowest PC1 values (1,2,4,5,6,7,10,11,13,17), corresponding to the most active compounds. The right side contains samples with the highest PC1 values (3,8,9,12,14,15,16,18,19,20), corresponding to the lowest active compounds.…”

Section: Principal Component Analysismentioning

confidence: 99%

“…All used activities in this report are logarithms of 1/IC 50 (−logIC 50 = pIC 50 ). In this work the compounds were considered according to the following criteria: compounds with pIC 50 < 8 43 mol/L (3,8,9,12,14,15,16,18,19,20) are the least potent compounds while those with pIC 50 ≥ 8 43 mol/L (1,2,4,5,6,7,10,11,13,17) are the most potent compounds.…”

Section: The Compounds Studiedmentioning

confidence: 99%

“…This will also allow for the Fe 2+ ion to attain a nearly octahedral hexacoordinated arrangement after binding to the artemisinin molecule. 13 For each ligand/receptor interaction, 100 (a hundred) conformations were calculated. Among the most frequent, the one with the lowest energy of interaction, which is considered the most favorable, was chosen to evaluate the Fe-O 1 and Fe-O 2 distances.…”

Section: Molecular Dockingmentioning

confidence: 99%

“…12 Calculations based on Density Functional Theory (DFT) have been a useful tool in investigating chemical structures, their interactions and consequently their biological properties such as in antimalarial mechanism. 13 14 Also it has been of great significance the use of quantitative structure-activity relationship (QSAR) for predicting new more potent molecules. [14][15][16][17][18][19][20][21][22][23] In a previous report on antimalarial artemisinin derivatives, MEP maps and molecular modeling have supported PLS results, revealing that higher values for HOMO energy combined with lower negative charge on oxygen atom, higher positive charge on carbon atom of the trioxane-ring system, higher values for the molecular volume and generally lower values for hydrophilic index increase antimalarial activity against P. falciparum.…”

Section: Introductionmentioning

confidence: 99%

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A Computational Study on Antimalarial Dispiro-1,2,4-Trioxolanes

Figueiredo¹,

Ferreira²,

Barbosa³

et al. 2011

Jnl of Comp & Theo Nano

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This work employed computational chemistry to study dispiro-1,2,4-trioxolanes with antimalarial activities against K-1 strains of Plasmodium falciparum. Molecules were optimized with B3LYP/6-31G* method. Maps of molecular electrostatic potential helped to identify features related to their activities. Molecular docking was performed to study the complex formed. A predictive model was generated by PLS method, with three latent variables explaining 99.8% of the total variance, Q 2 = 0 87, R 2 = 0 85, obtained for 16/4 molecules in the training/external validation set. The descriptors selected for the model were the binding free energy, logarithm of octanol-water partition coefficient (logP ) and molecular volume. As an application, we tested our PLS model to predict the pIC 50 of 20 dispiro-1,2,4-trioxolanes whose biological tests were not performed with them yet. Three compounds showed higher antimalarial activity than artemether and artesunate.

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Section: Principal Component Analysismentioning

confidence: 99%

Section: The Compounds Studiedmentioning

confidence: 99%

Section: Molecular Dockingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Computational Study on Antimalarial Dispiro-1,2,4-Trioxolanes

Figueiredo¹,

Ferreira²,

Barbosa³

et al. 2011

Jnl of Comp & Theo Nano

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“…Araújo et al [38] used density functional theory (6-31G*) to verify the performance of a base set in reproducing experimental data, particularly geometrical parameters, and to calculate the interaction energies, electronic states, and geometrical arrangements for complexes composed of a heme group and artemisinin. The results demonstrated that the interaction between artemisinin and the heme group occurs at long distances through a complex in which the iron atom of the heme group retains its electronic characteristics, with the quintet state being the most stable.…”

Section: Determination Of the Theoretical Geometrical Parameters For mentioning

confidence: 99%

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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Recyclization of 3‐substituted‐6,8‐dimethylchromones with some heterocyclic enamines: Spectroscopic, quantum calculations (HOMO–LUMO, MEP, NLO), biological evaluation, and ADME investigation

Badran,

Ibrahim

2024

Journal of Heterocyclic Chem

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The chemical reactivity of some 6,8‐dimethylchromones was studied toward certain heterocyclic enamines. Treatment of carboxaldehyde 1a with the certain enamines proceeded via condensation with concomitant γ‐pyrone ring opening. Reaction of carbonitrile 1b with enamine derivatives proceeded through opening of γ‐pyrone moiety associated with cycloaddition into the nitrile function. A novel angular chromenopyrazolopyridine and chromenopyridopyrimidines were efficiently synthesized from reacting carboxamide 1c with the current enamines. Moreover, frontier molecular orbitals analysis, electronegativity, global hardness, global softness, ionization energy, and HOMO‐LUMO energy gap were calculated by using DFT/B3LYP/6‐311++G(d,p) level. Using the GIAO approach, the 1H and 13C NMR spectra were calculated and showed good agreement with the experimental values. Additionally, the nonlinear optical (NLO) properties of the prepared compounds were found higher than urea. MEP was utilized to ascertain reactive sites within the molecules. The produced compounds exhibited varying degrees of inhibitory effect when tested for their antimicrobial and anticancer properties. The evaluation of ADME (absorption, distribution, metabolism, and excretion) parameters indicated good drug‐like properties of all the investigated compounds.

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Interaction between artemisinin and heme. A Density Functional Theory study of structures and interaction energies

Cited by 30 publications

References 32 publications

A Computational Study on Antimalarial Dispiro-1,2,4-Trioxolanes

A Computational Study on Antimalarial Dispiro-1,2,4-Trioxolanes

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

Recyclization of 3‐substituted‐6,8‐dimethylchromones with some heterocyclic enamines: Spectroscopic, quantum calculations (HOMO–LUMO, MEP, NLO), biological evaluation, and ADME investigation

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