Two-dimensional quantitative structure-activity relationship study of 1,4-naphthoquinone derivatives tested against...

A series of 50 derivatives of 1,4-naphthoquinone tested against human HL-60 leukaemic cells showed activity at a wide range of concentrations. A multivariate quantitative structure-activity relationship (QSAR) study of 45 compounds was performed through principal component analysis (PCA) and partial least squares (PLS) regression. A good PLS regression model was obtained with two factors describing 60.1% of the total variance, and the selected descriptors were partial atomic charge at carbons 1 and 10 (C1 and C10) and total dipole moment (DIP). The calibration model exhibited the determination coefficient r² = 0.78 and the standard error of calibration = 0.29. For external validation, r² and the standard error of prediction were 0.74 and 0.32, respectively. DIP and C1 were the main descriptors for PCA, as well as for PLS, such that the pIC₅₀ value increases when C1 increases and DIP diminishes. The selected descriptors are in accordance with the literature, once C10 and C1 are bound or close to the quinone oxygens involved in the production of radical anions (O₂-∙). From the QSAR analysis, the structures of two new naphthoquinones were proposed and their estimated IC₅₀ values were 1.42 and 1.13 μmol L^-1.