Quantitative Structure-Cytotoxicity Relationship of Chalcones.
Fifteen chalcones were subjected to quantitative structure-activity relationship (QSAR) analysis based on their cytotoxicity and tumor specificity, in order to find their new biological activities.



Cytotoxicity against four human oral squamous cell carcinoma cell lines and three oral mesenchymal cells was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated by the ratio of the mean 50% cytotoxic concentration (CC50) against normal cells to that against tumor cell lines. Potency-selectivity expression (PSE) value was calculated by dividing TS by CC50against tumor cells. Apoptosis markers were detected by western blot analysis. Physicochemical, structural and quantum-chemical parameters were calculated based on the conformations optimized by force-field minimization.



Among 15 chalcone derivatives, (2E)-1-(2,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one had the highest TS and PSE values, comparable with those of doxorubicin and methotrexate, respectively. This compound also stimulated the cleavage of poly(ADP-ribose) polymerase and caspase-3. Chalone TS values were correlated with molecular shape and polarization rather than the types of substituted groups. None of the compounds had any anti-HIV activity.



Chemical modification of the lead compound may be a potential choice for designing new types of anticancer drugs.
Division of Pharmacology, Meikai University School of Dentistry, Sakado, Japan sakagami@dent.meikai.ac.jp.|Meikai Pharmaco-Medical Laboratory (MPL), Meikai University School of Dentistry, Sakado, Japan.
Hiroshi
H
Sakagami
Meikai Pharmaco-Medical Laboratory (MPL), Meikai University School of Dentistry, Sakado, Japan.
Yoshiko
Y
Masuda
Meikai Pharmaco-Medical Laboratory (MPL), Meikai University School of Dentistry, Sakado, Japan.
Mineko
M
Tomomura
Division of Endodontics, Meikai University School of Dentistry, Sakado, Japan.
Satoshi
S
Yokose
Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
Yoshihiro
Y
Uesawa
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
Naruhiko
N
Ikezoe
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
Daiki
D
Asahara
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
Koichi
K
Takao
Department of Microbiology, St. Marianna University School of Medicine, Kanagawa, Japan.
Taisei
T
Kanamoto
Department of Microbiology, St. Marianna University School of Medicine, Kanagawa, Japan.
Shigemi
S
Terakubo
Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
Hajime
H
Kagaya
Department of Microbiology, St. Marianna University School of Medicine, Kanagawa, Japan.
Hideki
H
Nakashima
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
Yoshiaki
Y
Sugita
D019380:Anti-HIV Agents / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry*; D002648:Child; D004317:Doxorubicin / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D008727:Methotrexate / Q000737:chemistry; D009062:Mouth Neoplasms / Q000188:drug therapy; D021281:Quantitative Structure-Activity Relationship
D019380:Anti-HIV Agents; D000970:Antineoplastic Agents; D047188:Chalcones; D004317:Doxorubicin; D008727:Methotrexate
Chalcones; QSAR analysis; anti-HIV activity; apoptosis induction; cytotoxicity; tumor selectivity