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 (μ(x) ), Coulson charge (q(N) ) on the nitrogen atom sandwiched between the two substituted carbons of the triazine ring, and total energy (E(T) ) 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 R² value of 0.7697, and the squared cross-validated correlation coefficient R²(CV) value of 0.6469. The results are discussed in light of the main factors that influence the DHFR inhibitory activity.
Ojha
Himanshu
H
Department of Chemistry, University of Delhi, Delhi, India.
Gahlot
Pragya
P
Tiwari
Anjani K
AK
Pathak
Mallika
M
Kakkar
Rita
R
D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology; D003198:Computer Simulation; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000188:drug therapy; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*; D014227:Triazines / Q000138:chemical synthesis / Q000494:pharmacology
D000962:Antimalarials; D005493:Folic Acid Antagonists; D014227:Triazines; D013762:Tetrahydrofolate Dehydrogenase