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Anticancer Res. 2017 Mar;37(3):1091-1098.

Quantitative Structure-Cytotoxicity Relationship of Chalcones.

Author information

1
Division of Pharmacology, Meikai University School of Dentistry, Sakado, Japan sakagami@dent.meikai.ac.jp.
2
Meikai Pharmaco-Medical Laboratory (MPL), Meikai University School of Dentistry, Sakado, Japan.
3
Division of Endodontics, Meikai University School of Dentistry, Sakado, Japan.
4
Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
5
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Japan.
6
Department of Microbiology, St. Marianna University School of Medicine, Kanagawa, Japan.

Abstract

BACKGROUND:

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.

MATERIALS AND METHODS:

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 CC50 against 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.

RESULTS:

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.

CONCLUSION:

Chemical modification of the lead compound may be a potential choice for designing new types of anticancer drugs.

KEYWORDS:

Chalcones; QSAR analysis; anti-HIV activity; apoptosis induction; cytotoxicity; tumor selectivity

PMID:
28314269
DOI:
10.21873/anticanres.11421
[Indexed for MEDLINE]

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