Quantitative Structure Activity Relationship Study of 2,4,6-Trisubstituted-s-triazine Derivatives as Antimalarial Inhibitors of Plasmodium Falciparum Dihydrofolate Reductase

This study presents a quantitative structure activity relationships (QSAR) study on a pool of 19 bio‐active s‐triazine compounds. Molecular descriptors, kappa {1κ}, chi {3χ}, x component of the dipole moment (μx), Coulson charge (qN) on the nitrogen atom sandwiched between the two substituted carbon...

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Bibliographic Details
Published in:Chemical biology & drug design 2011-01, Vol.77 (1), p.57-62
Main Authors: Ojha, Himanshu, Gahlot, Pragya, Tiwari, Anjani K., Pathak, Mallika, Kakkar, Rita
Format: Article
Language:English
Subjects:
antifolates
antimalarials
Antimalarials - chemistry
Antimalarials - pharmacology
Computer Simulation
Folic Acid Antagonists - chemistry
Folic Acid Antagonists - pharmacology
GFA approach
Malaria, Falciparum - drug therapy
Models, Molecular
Plasmodium falciparum
Plasmodium falciparum - drug effects
QSAR
Quantitative Structure-Activity Relationship
s-triazines
Tetrahydrofolate Dehydrogenase - chemistry
Tetrahydrofolate Dehydrogenase - metabolism
Triazines - chemical synthesis
Triazines - pharmacology
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Summary:This study presents a quantitative structure activity relationships (QSAR) study on a pool of 19 bio‐active s‐triazine compounds. Molecular descriptors, kappa {1κ}, chi {3χ}, x component of the dipole moment (μx), Coulson charge (qN) on the nitrogen atom sandwiched between the two substituted carbons of the triazine ring, and total energy (ET) obtained from AM1 calculations provide valuable information and have a significant role in the assessment of dihydrofolate reductase (DHFR) inhibitory activity of the compounds. By using the Genetic Function Approach (GFA) technique, five QSAR models have been drawn up with the help of these calculated descriptors and DHFR inhibitory activity data of the molecules. Among the obtained QSAR models presented in the study, statistically the most significant one is a four‐parameter linear equation with the Lack‐of‐Fit value 0.5624, squared correlation coefficient R 2 value of 0.7697, and the squared cross‐validated correlation coefficient RCV2 value of 0.6469. The results are discussed in light of the main factors that influence the DHFR inhibitory activity.
ISSN:1747-0277
1747-0285
DOI:10.1111/j.1747-0285.2010.01045.x