Quantitative Structure-Cytotoxicity Relationship of Newly Synthesized Piperic Acid Esters
| Autor: | Takaki Miyashiro, Hajime Kagaya, Taisei Kanamoto, Junichi Murai, Yoshiko Masuda, Mineko Tomomura, Yoshihiro Uesawa, Hideki Nakashima, Shigemi Terakubo, Hiroshi Sakagami, Yoshiaki Sugita, Koichi Takao, Satoshi Yokose |
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| Rok vydání: | 2017 |
| Předmět: |
Cancer Research
Quantitative structure–activity relationship Stereochemistry Anti-HIV Agents Quantitative Structure-Activity Relationship Antineoplastic Agents Apoptosis chemistry.chemical_compound Humans Cytotoxicity Child Cells Cultured Cell Proliferation Mouth neoplasm Molecular Structure Chemistry Cell growth Chemical modification HIV Esters General Medicine Oncology Cell culture Carcinoma Squamous Cell Fatty Acids Unsaturated Female Mouth Neoplasms Lead compound Piperic acid |
| Zdroj: | Anticancer research. 37(11) |
| ISSN: | 1791-7530 |
| Popis: | BACKGROUND/AIM Eleven piperic acid 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 (CC50) against normal cells to that against tumor cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by CC50 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 One phenylmethyl ester and five phenylethyl esters showed relatively higher cytotoxicity and tumor specificity, that were significantly modified by introduction of hydroxyl and methoxy groups. On the other hand, phenylpropyl ester, phenylbutyl ester and decyl ester were essentially inactive. (2E,4E)-5-(3,4-methylenedioxyphenyl)-2,4-pentadienoic acid 2-(3,4-dihydroxyphenyl)ethyl ester [4] had the highest TS and PSE values. This compound also stimulated the cleavage of caspase-3, suggesting the induction of apoptosis. TS values were correlated with molecular size, ionization potential, molecular shape, ionization potential and electronegativity. None of the compounds had any anti-HIV activity. CONCLUSION Chemical modification of the lead compound may be a potential choice for designing a new type of anticancer drugs. |
| Databáze: | OpenAIRE |
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