RRC ID 45152
著者 Shimada C, Uesawa Y, Ishihara M, Kagaya H, Kanamoto T, Terakubo S, Nakashima H, Takao K, Saito T, Sugita Y, Sakagami H.
タイトル Quantitative structure-cytotoxicity relationship of phenylpropanoid amides.
ジャーナル Anticancer Res
Abstract BACKGROUND:A total of 12 phenylpropanoid amides were subjected to quantitative structure-activity relationship (QSAR) analysis, based on their cytotoxicity, tumor selectivity and anti-HIV activity, in order to investigate on their 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 CC50 (50% cytotoxic concentration) against normal oral cells to that against OSCC cell lines. Anti-HIV activity was evaluated by the ratio of CC50 to EC50 (50% cytoprotective concentration from HIV infection). Physicochemical, structural, and quantum-chemical parameters were calculated based on the conformations optimized by the LowModeMD method followed by density functional theory (DFT) method.
RESULTS:Twelve phenylpropanoid amides showed moderate cytotoxicity against both normal and OSCC cell lines. N-Caffeoyl derivatives coupled with vanillylamine and tyramine exhibited relatively higher tumor selectivity. Cytotoxicity against normal cells was correlated with descriptors related to electrostatic interaction such as polar surface area and chemical hardness, whereas cytotoxicity against tumor cells correlated with free energy, surface area and ellipticity. The tumor-selective cytotoxicity correlated with molecular size (surface area) and electrostatic interaction (the maximum electrostatic potential).
CONCLUSION:The molecular size, shape and ability for electrostatic interaction are useful parameters for estimating the tumor selectivity of phenylpropanoid amides.
巻・号 34(7)
ページ 3543-8
公開日 2014-7-1
PII 34/7/3543
PMID 24982367
MeSH Amides / chemistry* Amides / pharmacology* Anti-HIV Agents / chemistry* Anti-HIV Agents / pharmacology* Antineoplastic Agents / chemistry* Antineoplastic Agents / pharmacology* Benzylamines / chemistry Benzylamines / pharmacology Carcinoma, Squamous Cell / drug therapy Child Dopamine / analogs & derivatives Dopamine / pharmacology Female Head and Neck Neoplasms / drug therapy Humans Mouth Neoplasms / drug therapy Quantitative Structure-Activity Relationship Squamous Cell Carcinoma of Head and Neck Tyramine / analogs & derivatives Tyramine / pharmacology
IF 1.994
引用数 8
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 Ca9-22(RCB1976) HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902)