Background: Since flavonoids fused by benzene have been known for their potent chemopreventive
effects, in this study, we examined the relationship between the structures and activities
of benzoflavones, benzoflavanones, benzochalcones, and benzochalcone derivatives bearing the
pyrazole moiety against human colon cancer cells.
Methods: We investigated the effect of 34 benzoflavonoids on the inhibition of colon cancer cells
based on the clonogenicity. The biological activity values used for the quantitative structure-activity
relationship (QSAR) calculations were obtained from the cell growth inhibition on the basis of
clonogenicity. 3D-QSAR calculations were performed using comparative molecular field analyses
(CoMFA) and comparative molecular similarity index analyses (CoMSIA).
Results: Of several CoMFA and CoMSIA models, the best models showing the highest cross validated
correlation coefficient were selected and validated. The cell growth inhibition values were calculated
using the above models. The structural conditions to show good cell growth inhibitory effects
on human colon cancer cells were analyzed by CoMFA and CoMSIA contour maps. The contribution
of steric fields remarkably decreased without any change in the contribution of the electrostatic
field, which means that electrostatic contribution is more crucial than the steric contribution in the
modification of benzoflavonoids. Furthermore, the increase in the hydrogen bond donor contribution
was approximately proportional to the decrease in steric field contribution.
Conclusion: This study demonstrated that benzoflavonoids structure hinders colon cancer clonogenicity.
Most of the benzoflavonoids structures comprised a C-3 linkage between the naphthalene
and phenyl moieties, which contained diverse functional moieties such as oxygen-fused rings, double
bonds, pyrazole rings, and sulfur constituents, and were able to exhibit great potential in diverse anticancer
effects. Also, the positions of the hydroxyl group close to the naphthalene and phenyl rings
were crucial for activity against colon cancer. The structural conditions obtained here may help us
design potent benzoflavonoids against colon cancer cells and predict their activities.