Quantitative Structure-Cytotoxicity Relationship of Cinnamic Acid Phenetyl Esters.

Background/aim: Many phenolic acid phenethyl esters possess diverse biological effects including antioxidant, cytoprotective, anti-inflammation and anti-tumor activities. However, most previous antitumor studies have not considered the cytotoxicity against normal cells. Ten cinnamic acid phenetyl esters were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity and tumor-specificity, in order to find their new biological activities.
Materials and Methods: Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral normal mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC ₅₀ ) against normal oral cells to that against human oral squamous cell carcinoma cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by CC ₅₀ against tumor cells. Apoptosis markers were detected by western blot analysis. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by force-field minimization.
Results: Western blot analysis demonstrated that [ 9 ] stimulated the cleavage of caspase-3, suggesting the induction of apoptosis. QSAR analysis demonstrated that TS values were correlated with shape, size and ionization potential.
Conclusion: Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs.
(Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)