Quantitative structure-cytotoxicity relationship of piperic acid amides

• Published in: Anticancer research Vol. 34; no. 9; p. 4877
• Main Authors: Shimada, Chiyako, Uesawa, Yoshihiro, Ishihara, Mariko, Kagaya, Hajime, Kanamoto, Taisei, Terakubo, Shigemi, Nakashima, Hideki, Takao, Koichi, Miyashiro, Takaki, Sugita, Yoshiaki, Sakagami, Hiroshi
• Format: Journal Article
• Language: English
• Published: Greece 01.09.2014
• Subjects: Amides - chemistry; Amides - toxicity; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Cell Line; Cell Line, Tumor; Fatty Acids, Unsaturated - chemistry; Humans; Inhibitory Concentration 50; Microbial Sensitivity Tests; Molecular Structure; Quantitative Structure-Activity Relationship; tumor selectivity; QSAR analysis; anti-HIV activity; Piperic acid amides; cytotoxicity
• ISSN: 1791-7530; 1791-7530

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. 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. 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. The present study suggests that molecular shape and ability for electrostatic interaction are useful parameters for estimating the tumor selectivity of piperic acid amides.