title: Quantitative structure-cytotoxicity relationship of piperic acid amides.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors.forename: Chiyako
authors.initials: C
authors.lastname: Shimada
authors.affiliation: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uesawa
authors.affiliation: Division of Basic Chemistry, Meikai University School of Dentistry, Sakado, Saitama, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Noshio, Kiyose, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kagaya
authors.affiliation: St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Taisei
authors.initials: T
authors.lastname: Kanamoto
authors.affiliation: St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Shigemi
authors.initials: S
authors.lastname: Terakubo
authors.affiliation: St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakashima
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takao
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Takaki
authors.initials: T
authors.lastname: Miyashiro
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sugita
authors.affiliation: Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan sakagami@dent.meikai.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000633:toxicity*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D005231:Fatty Acids, Unsaturated; C017637:piperic acid
keywords: Piperic acid amides; QSAR analysis; anti-HIV activity; cytotoxicity; tumor selectivity