Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
Anticancer Res. 2014 Sep;34(9):4877-84.
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.
为了寻找新的生物活性，对包括胡椒碱在内的 12 种胡椒基酰胺进行了定量构效关系（QSAR）分析，基于它们的细胞毒性、肿瘤选择性和抗 HIV 活性。
采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法测定对 4 个人口腔鳞状细胞癌（OSCC）细胞系和 3 个人口腔正常细胞的细胞毒性。肿瘤选择性通过正常口腔细胞与 OSCC 细胞系的平均 50%细胞毒性浓度（CC50）之比来评估。抗 HIV 活性通过 CC50 与 50%HIV 感染细胞保护浓度（EC50）之比来评估。根据 LowModeMD 方法优化后的构象计算理化、结构和量子化学参数，然后采用密度泛函理论方法。
所有化合物均表现出低至中度的肿瘤选择性，但没有抗 HIV 活性。具有儿茶酚部分的 N-胡椒酰多巴胺（8：）显示出最高的肿瘤选择性，可能是由于其独特的分子形状和静电相互作用，特别是其最大的轨道电负性和 vsurf 描述符的部分均衡。
本研究表明，分子形状和静电相互作用能力是估计胡椒基酰胺肿瘤选择性的有用参数。
