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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. December 2006, Volume 5, Number 12, 555-569 |
Quantitative Structure–Activity Relationships of a Series of Chalcone Derivatives
(1,3–Diphenyl–2–propen–1–one) as Anti Plasmodium falciparum Agents (Anti Malaria Agents)
Luiz Frederico Motta, Anderson Coser Gaudio, and Yuji Takahata
Internet Electron. J. Mol. Des. 2006, 5, 555-569
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Abstract:
Malaria is globally recognized as serious problem of public health,
mainly in the tropical and subtropical regions of the world. The
increase of resistant malarial parasite strains represents the largest
obstacle to antimalarial chemotherapy. In this work, we studied
chalcone derivatives, because they present wide range of biological
activity and a supposed mechanism of action: inhibition of malarial
cysteine protease. QSAR analysis was performed on the series of
chalcone derivatives. Various physical-chemical parameters such as
hydrophobic, electronic, steric, thermodynamic and structural were
calculated using computational package Molecular Modeling Pro 4.0,
ChemSite Pro 5.0 and Arguslab 4.0 programs. QSAR models with up
to four variables were generated employing multiple linear regression
method using BuildQSAR program. Statistically significant models
with R–values 0.931 and 0.958 were obtained. Results obtained show
that hydrophobic and steric properties seem to play an important role
in the explanation of the activity. Molar refractivity and molecular
length have positive contribution to the activity against chloroquine–resistant
(W2) Plasmodium falciparum strains, while molecular weight
against mefloquine–resistant (D6) strains. The results indicated that
the activity against W2 and D6 strains is favored if ring A is a width–
limited chemical substituent and the limited molecular width of these
derivatives can be related with the activity against D6 strain. The
present QSAR study reveal descriptors that may be important in the
inhibitory activity of chalcone derivatives on P. falciparum cysteine
protease. We obtained two different models against Plasmodium
falciparum strains. The models have good capacity to explain the
observed values of biological activity, good adjustment level,
statistical significance and good predictive capacity.
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