Aim: Sixteen 3-benzylidenechromanones were
subjected to quantitative structure–activity relationship (QSAR)
analysis based on their cytotoxicity and tumor-specificity, in
order to examine their new biological activities. Materials and
Methods: Cytotoxicity against two human oral squamous cell
carcinoma cell lines, two mesenchymal and two epithelial
normal oral cells, was determined by the 3-(4,5-dimethylthiazol-
2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-specificity
(TS) was evaluated by the ratio of the mean CC50 (50%
cytotoxic concentration) against normal cells to that against
tumor cell lines. Physicochemical, structural and quantumchemical
parameters were calculated based on the
conformations optimized by the LowModeMD method. Results:
3-Benzylidenechromanone derivatives that have a methoxy group
at 7-position of the chromanone ring and hydroxyl or methoxy
group at 4’-position of benzene ring showed relatively higher TS
values, exceeding those of doxorubicin (DXR) and 5-fluorouracil
(5-FU). Since these anticancer drugs were highly cytotoxic to
normal keratinocytes, QSAR analysis was performed with oral
carcinoma and mesenchymal normal cells. Tumor-specificity was
well correlated with 3D-MoRSE descriptors (that relate to three
dimensional shapes) and Edge adjacency indices (that relate to
two dimensional shapes and polarization). Introduction of
hydroxyl group at 3’-position of benzene ring significantly
elevated the tumor-specificity. Conclusion: Molecular shape, size
and polarization are useful markers for the evaluation of tumorspecificity
of 3-benzylidenechromanone derivatives.