Quantitative Structure-cytotoxicity Relationship of 3-Benzylidenechromanones.

Abstract

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 quantum-chemical 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 tumor-specificity of 3-benzylidenechromanone derivatives.

• Authors: Yoshihiro Uesawa, Hiroshi Sakagami, Hajime Kagaya, Marimo Yamashita, Koichi Takao, Yoshiaki Sugita
• Journal: Anticancer research (Anticancer Res) Vol. 36 Issue 11 Pg. 5803-5812 (11 2016) ISSN: 1791-7530 [Electronic] Greece
• PMID: 27793902 (Publication Type: Journal Article)
• Copyright: Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Chemical References

• Isoflavones

Topics

• Carcinoma, Squamous Cell (pathology)
• Cell Line, Tumor
• Drug Screening Assays, Antitumor
• Humans
• Isoflavones (chemistry, pharmacology)
• Quantitative Structure-Activity Relationship