Abstract | BACKGROUND: A total of 12 piperic acid amides, including piperine, were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to find new biological activities. MATERIALS AND METHODS: Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor selectivity was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of the CC50 to 50% HIV infection-cytoprotective concentration (EC50). Physicochemical, structural, and quantum-chemical parameters were calculated based on the conformations optimized by LowModeMD method followed by density functional theory method. RESULTS: All compounds showed low-to-moderate tumor selectivity, but no anti-HIV activity. N-Piperoyldopamine ( 8: ) which has a catechol moiety, showed the highest tumor selectivity, possibly due to its unique molecular shape and electrostatic interaction, especially its largest partial equalization of orbital electronegativities and vsurf descriptors. CONCLUSION: The present study suggests that molecular shape and ability for electrostatic interaction are useful parameters for estimating the tumor selectivity of piperic acid amides.
|
Authors | Chiyako Shimada, Yoshihiro Uesawa, Mariko Ishihara, Hajime Kagaya, Taisei Kanamoto, Shigemi Terakubo, Hideki Nakashima, Koichi Takao, Takaki Miyashiro, Yoshiaki Sugita, Hiroshi Sakagami |
Journal | Anticancer research
(Anticancer Res)
Vol. 34
Issue 9
Pg. 4877-84
(Sep 2014)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 25202069
(Publication Type: Journal Article)
|
Copyright | Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved. |
Chemical References |
- Amides
- Anti-HIV Agents
- Fatty Acids, Unsaturated
- piperic acid
|
Topics |
- Amides
(chemistry, toxicity)
- Anti-HIV Agents
(chemistry, pharmacology)
- Cell Line
- Cell Line, Tumor
- Fatty Acids, Unsaturated
(chemistry)
- Humans
- Inhibitory Concentration 50
- Microbial Sensitivity Tests
- Molecular Structure
- Quantitative Structure-Activity Relationship
|