title: Quantitative structure-cytotoxicity relationship of phenylpropanoid amides.
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.
  
  
  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).
  
  
  CONCLUSIONS
  The molecular size, shape and ability for electrostatic interaction are useful parameters for estimating the tumor selectivity of phenylpropanoid amides.
authors: Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors: Chiyako
authors: C
authors: Shimada
authors: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
authors: Yoshihiro
authors: Y
authors: Uesawa
authors: Basic Chemistry, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors: Mariko
authors: M
authors: Ishihara
authors: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
authors: Hajime
authors: H
authors: Kagaya
authors: St. Marianna University School of Medicine, Kanagawa, Japan.
authors: Taisei
authors: T
authors: Kanamoto
authors: St. Marianna University School of Medicine, Kanagawa, Japan.
authors: Shigemi
authors: S
authors: Terakubo
authors: St. Marianna University School of Medicine, Kanagawa, Japan.
authors: Hideki
authors: H
authors: Nakashima
authors: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors: Koichi
authors: K
authors: Takao
authors: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors: Takayuki
authors: T
authors: Saito
authors: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors: Yoshiaki
authors: Y
authors: Sugita
authors: Division of Pharmacology, Department of Diagnostic and Therapeutic Sciences, Meikai University School of Dentistry, Sakado, Saitama, Japan sakagami@dent.meikai.ac.jp.
authors: Hiroshi
authors: H
authors: Sakagami
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001596:Benzylamines / Q000737:chemistry / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002648:Child; D004298:Dopamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship; D000077195:Squamous Cell Carcinoma of Head and Neck; D014439:Tyramine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D001596:Benzylamines; D004298:Dopamine; D014439:Tyramine
keywords: Phenylpropanoid amides; QSAR analysis; anti-HIV activity; cytotoxicity; tumor selectivity