Abstract.
AM1 semiempirical molecular orbital calculations were carried out on lapachol and several derivatives of 1,4-naphthoquinone in order to investigate possible relationships between electronic structural parameters and activity against carcinosarcoma Walker 256 (W256). It was found that, among the calculated electronic indices, that the HOMO (highest occupied molecular orbital) coefficients for carbon atoms of the side-chain double bond have a significant influence in the activity, while the LUMO (lowest unoccupied molecular orbitals) apparently have no importance. Exploratory data analysis through hierarchical cluster (HCA) and principal component analysis (PCA) showed a clear separation of the active compounds from the inactive ones. The activity against W256 probably involves a mechanism wherein the quinone acts as a reducing agent through the participation of the p-electrons of the side-chain double bond. A classification study with respect to structure-activity using KNN (K-nearest neighbors) and SIMCA (soft independent modeling of class analogy), two established chemometric methods of pattern recognition, have been used to predict activity for a series of lapachol derivatives.

Keywords.
MNDO; AM1; SCF-MO; Lapachol; PCA; HCA; KNN; SIMCA.

Keywords Plus.
Pattern Recognition; Quinones.