Estudo teórico da interação existente entre a artemisinina e o heme

Costa, Mírian da Silva; Kiralj, Rudolf; Ferreira, Márcia M. C.

doi:10.1590/s0100-40422007000100006

Cited by 11 publications

(12 citation statements)

References 29 publications

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“…This interaction for compounds 2 and 14, the most active and the least active in the training set, respectively, is visualized in Fig. 40 Moreover substituent and conformation effects may affect the charge distribution at the oxygen and even the Fe-O 1 bond. Such orientations were assumed as the most favorable and so represent the real system under investigation, considering they were chosen based on the lowest free-energy of binding (interaction energy).…”

Section: Molecular Dockingmentioning

confidence: 95%

A study of new antimalarial artemisinins through molecular modeling and multivariate analysis

Ferreira¹,

Figueiredo²,

Barbosa³

et al. 2010

JSCS

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Artemisinin and 18 derivatives with antimalarial activity against W-2 strains of Plasmodium falciparum were studied through quantum chemistry and multivariate analysis. The geometry optimization of the structures was realized with the Hartree-Fock (HF) theory and 3-21G basis set. Maps of molecular electrostatic potential (MEP) and molecular docking were used to investigate the interaction between the ligands and the receptor (heme). Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were employed to select the most important descriptors related to activity. A predictive model was generated by the Partial Least Square (PLS) method through 15 molecules and 4 used as an external validation set, which were selected in the training set, the validation parameters of which are Q2 = 0.85 and R2 = 0.86. The model included as molecular parameters, the radial distribution function, RDF060e, the hydration energy, HE, and the distance between the O1 atom from the ligand and the iron atom from heme, d(Fe-O1). Thus, the synthesis of new derivatives may follow the results of the MEP maps and the PLS analysis

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Section: Molecular Dockingmentioning

confidence: 95%

A study of new antimalarial artemisinins through molecular modeling and multivariate analysis

Ferreira¹,

Figueiredo²,

Barbosa³

et al. 2010

JSCS

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“…First, to validate the CONFLEX routine, a complex with the same CAFeAO 1 AO 2 dihedral angle of 51.90 obtained by previous systematic conformational analysis [40] was constructed and compared with our final complex. The RMSD value between these structures is 0.78 Å meaning that CONFLEX is an efficient tool in docking process when is necessary to apply an exhaustive search for minimal structures.…”

Section: Resultsmentioning

confidence: 99%

Search for new antimalarial compounds obtained from natural sources by molecular modeling

Leite

Taranto

Santos

et al. 2010

Int J of Quantum Chemistry

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Artemisinin is a sesquiterpene lactone with an endoperoxide function that is currently being used against strains of Plasmodium falciparum. Endoperoxides are supposed to act on heme leading to reduction of the peroxide bond and production of radicals that can kill the parasite. As artemisinin, other natural compounds have the peroxide group and may also show antimalarial activity. This fact motivated us to study the interaction of 18 peroxides natural Brazilian flora with the heme group and compared with the values obtained for artemisinin. Initially, a conformational search was performed using the MM3 method for each molecule. The most stable conformers were optimized by the PM3(tm) method. Then, there was a docking between the peroxide and the heme group, again followed by a conformational search. Finally, the complex was optimized to obtain highest occupied molecular orbital, lowest unoccupied orbital, and molecular electrostatic potential (MEP) by the PM3(tm) method. All these calculations were performed using the Titan package. Among the natural peroxides, we studied (18), four have molecular orbital, MEP, and interaction energies similar to artemisinin. INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY 2059 structure was refined by MM3 [32-34] using steep-descent following conjugated gradient. As heme has flexible side chains, an exhaustive search for the global minimum was performed by the CONFLEX routine [35]. CONFLEX can generate a conformation data base with respective heat of formation using the MM3 method. The lower energy conformer was refined by the semiempirical PM3tm method [36], using default routines. The same process was carried out for all natural peroxides (see Fig. 3), including artemisinin. All peroxides were optimized by MM3, submitted to FIGURE 2. Heme group complexed with one water molecule. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com.]FIGURE 3. Selected natural peroxides. LEITE ET AL.

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“…Portanto, a investigação em maior detalhe de tais interações no complexo é importante do ponto de vista do reconhecimento molecular do heme com respeito à artemisinina. (COSTA et al, 2007).…”

Section: Mecanismo De Ação Da Artemisininaunclassified

Revisão de literatura sobre o mecanismo de ação da artemisinina e dos endoperóxidos antimaláricos - parte II

Almeida¹,

Santos²,

Santana³

et al. 2016

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Artemisinina é uma lactona sesquiterpênica com um grupamento endoperóxido, a qual vem sendo usada contra cepas de Plasmodium falciparum resistentes ao tratamento com cloroquina. Os compostos endoperóxidos agem supostamente no grupo heme levando à redução da ligação peróxido e produção de radicais que podem matar o parasito. Estudos recentes mostraram que a artemisinina pode inibir a enzima ATPase cálcio-dependente (PfATP6) localizada no retículo sarco/endoplasmático, ou seja, fora do vacúolo do parasito Plasmodium falciparum. Atualmente, a malária mata mais do que a AIDS e o pressuposto da crescente resistência adquirida pelo parasito aos fármacos atuais endossa a necessidade pela busca de novas alternativas terapêuticas. Para a realização do estudo foi feito um levantamento bibliográfico nos principais livros e periódicos indexados no portal CAPES. A artemisinina e os endoperóxidos são representantes de uma nova classe de fármacos antimaláricos. Devido à resistência adquirida pelo parasito aos derivados quinolínicos, a artemisinina e seus derivados estão sendo empregados como terapia de escolha para o tratamento de malária. O mecanismo de ação destas substâncias, embora ainda não totalmente esclarecido, é completamente diferente dos antimaláricos convencionais, sendo, portanto, uma nova esperança para o tratamento da malária. Este artigo é a segunda parte de uma revisão sobre o provável mecanismo de ação dos endoperóxidos antimaláricos. Palavras

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Estudo teórico da interação existente entre a artemisinina e o heme

Cited by 11 publications

References 29 publications

A study of new antimalarial artemisinins through molecular modeling and multivariate analysis

A study of new antimalarial artemisinins through molecular modeling and multivariate analysis

Search for new antimalarial compounds obtained from natural sources by molecular modeling

Revisão de literatura sobre o mecanismo de ação da artemisinina e dos endoperóxidos antimaláricos - parte II

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