3D-QSAR analysis of cycloguanil derivatives, highly active agents against A16V + S108T mutant of dihydrofolate reductase resistant strain (T9/94) of Plasmodium falciparum

Abstract

3D-Quantitative-structure activity relationship of some 4,6-diamino-1,2-dihydrotriazine derivatives (cycloguanils) having good activity against resistant strain of P. falciparum has been performed. The model developed has shown that the descriptors, ovality (steric descriptor), dipole-dipole energy (thermodynamic descriptor) contributing positively while stretch bend energy (thermodynamic descriptor) negatively to the biological activity. Statistical analysis has shown the model to be fit (R=0.924, R²=0.853, F-test=18.840, t-test=4.340, stdev = 0.244, variance=0.051) and predictable (R²ւօօ=0.693, R²pred=0.265). It can be concluded that parent nuclei having functional groups with optimum values for these descriptors, might have better biological activity against resistant strains.