Quantitative Structure-Cytotoxicity Relationship of Cinnamic Acid Phenetyl Esters

• Published in: Anticancer research 2018-02, Vol.38 (2), p.817
• Main Authors: Uesawa, Yoshihiro, Sakagami, Hiroshi, Okudaira, Noriyuki, Toda, Kazuhiro, Takao, Koichi, Kagaya, Hajime, Sugita, Yoshiaki
• Format: Article
• Language: English
• Subjects: Anticancer properties; Antineoplastic drugs; Antioxidants; Antitumor agents; Apoptosis; Biological effects; Biological materials; Biotechnology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Caspase; Caspase-3; Cell Line, Tumor; Chemical modification; Child; Cinnamates - chemistry; Cinnamates - pharmacology; Cinnamates - toxicity; Cinnamic acid; Cytotoxicity; Dental materials; Esters; Esters - chemistry; Esters - pharmacology; Esters - toxicity; Fibroblasts - drug effects; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - pathology; Humans; Ionization; Ionization potentials; Lead compounds; Male; Materials selection; Mathematical analysis; Mesenchyme; Mouth Neoplasms - drug therapy; Mouth Neoplasms - pathology; Oral cancer; Oral squamous cell carcinoma; Organic chemistry; Phenolic acids; Phenols; Phenylethyl Alcohol - chemistry; Phenylethyl Alcohol - pharmacology; Phenylethyl Alcohol - toxicity; Quantitative Structure-Activity Relationship; Quantum chemistry; Selectivity; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Structure-activity relationships; Toxicity; Tumor cell lines; Tumor cells; Tumors
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.12289

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. 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 ) 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 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. Western blot analysis demonstrated that [ ] 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. Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs.