Antimalarial activity of dihydroartemisinin derivatives against P. falciparum resistant to mefloquine: a quantum chemical and multivariate study

Pinheiro, José; Ferreira, Márcia M. C.; Romero, Oscar A. S.

doi:10.1016/s0166-1280(01)00522-x

Cited by 22 publications

(13 citation statements)

References 19 publications

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“…In spite of the general opinion that the structures of AcrB antibiotic drug substrates have not much in common, this study relied on structure and structural characteristics (molecular descriptors) of the substrates, which definitely determine their physical characteristics and biochemical behavior. This approach is in accord with quantitative structure-activity relationship (QSAR) [22][23][24][25][26][27][28][29] and structure-activity relationship (SAR) [30][31][32] studies recently performed in our group on various classes of drugs. The QSAR study in this work was performed by means of the partial least squares (PLS) [33][34][35][36] method.…”

Section: Introductionmentioning

confidence: 85%

QSAR study of β‐lactam antibiotic efflux by the bacterial multidrug resistance pump AcrB

Ferreira

Kiralj

2004

Journal of Chemometrics

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AcrAB-TolC is the most important efflux pump system of Gram-negative bacteria, responsible for their resistance to lipophilic and amphilic drugs. In this work, HCA-PCA studies were performed to investigate the relationship between efflux activities (negative logarithm of minial inhibitor concentration, pMIC) of three strains of S. thypimurium with respect to b-lactams, and to analyze the relationship between lipophilicity parameters calculated by different methods. The analyses demonstrate that pMICs strongly depend on properties of both bacterial strains and drug molecules, and that lipophilicity parameters do not necessarily contain the same information about the drugs. QSAR studies have shown that the calculated lipophilicities, in some cases, are non linearly related to the pMICs originated by active AcrAB-TolC bacterial pumps, due to the existence of b-lactams with nitrogen-and sulfur-rich substituents. Among the most important b-lactam molecular properties quantitatively related to pMICs are lipophilicity and electronic and hydrogen-bonding properties. Parameters describing these properties were included in the QSAR study to obtain parsimonius regression models for MICs. b-Lactams were classified as good, moderately good and poor AcrABTolC substrates. Their stereoelectronic molecular properties, especially the Y-component of the molecular dipole moment and hydrogen binding properties, reflected this classification.

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Section: Introductionmentioning

confidence: 85%

QSAR study of β‐lactam antibiotic efflux by the bacterial multidrug resistance pump AcrB

Ferreira

Kiralj

2004

Journal of Chemometrics

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“…The MEP, Homo and Lumo were visualized and calculated using HartreeFock (HF) method and HF/6-31G** basis set by the Molekel program [24]. two (2) compounds of a set of twelve (12) test predicted as of high activity were proposed [19]. Artemisinin derivatives with antimalarial activity against Plasmodium falciparum, which is resistant to mefloquine, were studied using quantum chemical methods (HF/6-31G*) and the partial least-squares (PLS) method.…”

Section: (B) Map Of Molecular Electrostatic Potential (Mep) ((C) Andmentioning

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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“…Geometrically, this transformation represents rotation of the original coordinate system, so that the direction of the maximum residual variance is given by the first principal component axis. The second principal component axis, orthogonal to the first one, has the second maximum variance and so on [34,35]. The PCA method was used in order to obtain a separation of the set of compounds in two groups (actives and inactives), according to the calculated molecular descriptors.…”

Section: Pcamentioning

confidence: 99%

A quantum chemical and chemometric study of sesquiterpene lactones with cytotoxicity against tumor cells

Arantes

Barbosa

Maltha

et al. 2011

Journal of Chemometrics

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The semi-empirical molecular orbital method PM6 was employed to calculate a set of molecular descriptors of 20 sesquiterpene lactones (SQLs) with cytotoxicity against HL-60 (leukemia) tumor cells. The principal component analysis (PCA) and hierarchical cluster analysis (HCA) methods were used to obtain possible relationships between the calculated descriptors and the biological activity of the lactones. Four descriptors were identified as responsible for the separation between the active and inactive compounds: E HOMO (highest occupied molecular orbital energy); Q11 (net atomic charge on C11); Q12 (net atomic charge on C12) and Q13 (net atomic charge on C13). These results indicated that the presence of the a-methylene-g-lactone group has a significant role in the mechanism by which SQLs exert their biological activities.

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Antimalarial activity of dihydroartemisinin derivatives against P. falciparum resistant to mefloquine: a quantum chemical and multivariate study

Cited by 22 publications

References 19 publications

QSAR study of β‐lactam antibiotic efflux by the bacterial multidrug resistance pump AcrB

QSAR study of β‐lactam antibiotic efflux by the bacterial multidrug resistance pump AcrB

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

A quantum chemical and chemometric study of sesquiterpene lactones with cytotoxicity against tumor cells

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