Pereira F. S., Martins J. P. A., de Melo E. B., Ferreira M. M. C., "2D-QSAR Analysis of aziridinyl-1,4-naphthoquinone Antimalarials Using Partial Least Square (PLS)". São Pedro, SP, Brazil, 12-15/11/2006: The 3rd Brazilian Symposium on Medicinal Chemistry: Recent Advances in Drug Discovery and Development. Abstract Book, (2006) S1-037. Poster S1-037. Session: Drug Discovery and Development: Sci-Mix.

Key words: QSAR, antimalarial, PLS
2D-QSAR models employing the PLS regression were built for a set of aziridinyl-1,4-naphthoquinones with antimalarial activity from literature, using several molecular descriptors calculated by PM3 method. The most relevant descriptors to the biological activity were the Gibbs Fee-Energy in the Vacuum (GFEv) and the partial atomic charges Qa, Qc and Qh (R² = 0.896; Q² = 0.884; R²_w = 0.514). The presence of the GFEv, Qc and Qa descriptors in the model show the importance of the quinone ring's reduction for the antimalarial activity, what is in agreement with the literature. The R₂ substituent is and H or an aziridinyl ring, Qh is the partial charge of this H or of the N in the ring, Qa is the partial charge of carbonyl oxygen and Qc is the partial charge of carbon c. In the most active compounds, the R₂ substituent is the H indicating that steric descriptors for the H and the aziridinyl could be relevant for building up a new model. The inclusion of molar refractivity would take into account electronic and steric effects improved slightly the model (R² = 0.906; Q² = 0.877; R²_w = 0.718). The exclusion of the Qh descriptor significantly worsened the model (Q² = 0.086). These are strong evidences that, the steric effect allied to a sharp electronic effect in R₂ probably affects the antimalarial activity of the investigated set of compounds.
 
 

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