Catalyst/HypoGen phar
macophore
modeling approach and three-di
mensional quantitative structure-activityrelationship (3D-QSAR)/co
mparative
molecular si
milarity indices analysis (CoMSIA)
methods have beensuccessfully applied to explain the cytotoxic activity of a set of 51 natural and synthesized naphthoquinonederivatives tested in hu
man pro
myelocytic leuke
mia HL-60 cell line. The co
mputational
models havefacilitated the identification of structural ele
ments of the ligands that are key for antitu
moral properties. Thefour
most salient features of the highly active
![](/i<font color=)
mages/gifchars/beta2.gif" BORDER=0 ALIGN="
middle">-cycled-pyran-1,2-naphthoquinones [0.1
![](/i<font color=)
mages/entities/
mgr.gif">M < IC
50 < 0.6
![](/i<font color=)
mages/entities/
mgr.gif">M] are the hydrogen-bond interactions of the carbonyl groups at C-1 (HBA1) and C-2 (HBA2), the hydrogen-bond interaction of the oxygen ato
m of the pyran ring (HBA3), and the interaction of
methyl groups (HYD)at the pyran ring with a hydrophobic area at the receptor. The
moderately active 1,4-naphthoquinonederivatives accurately fulfill only three of these features. The results of our study provide a valuable tool indesigning new and
more potent cytotoxic analogues.