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In Vivo. 2018 May-Jun;32(3):479-486.

In Vitro Anti-tumor Activity of Azulene Amide Derivatives.

Author information

1
Faculty of Science, Josai University, Saitama, Japan.
2
Faculty of Science, Josai University, Saitama, Japan hwaka@josai.ac.jp sakagami@dent.meikai.ac.jp.
3
Division of Pharmacology, Meikai University School of Dentistry, Saitama, Japan.
4
Department of Clinical Pharmaceutics, Meiji Pharmaceutical University, Tokyo, Japan.
5
Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan hwaka@josai.ac.jp sakagami@dent.meikai.ac.jp.

Abstract

BACKGROUND/AIM:

There exist few research articles regarding the anticancer activity of azulene-related compounds. We investigated here the relative cytotoxicity of 10 azulene amide derivatives against cancer and normal cells.

MATERIALS AND METHODS:

Cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and three human oral normal cells (gingival fibroblasts, periodontal ligament fibroblasts and pulp cells) was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide method. Antitumor activity was evaluated by tumor-specificity (TS) (ratio of mean 50% cytotoxic concentration (CC50) against normal cells to that against OSCC cell lines) and potency-selectivity expression (PSE) (ratio of TS to CC50 against tumor cells). Apoptosis-inducing activity was evaluated by cleavage of poly ADP-ribose polymerase and caspase-3 with western blot analysis.

RESULTS:

N-Propylguaiazulenecarboxamide [1] showed the highest TS and PSE values, compared to that of doxorubicin, and induced apoptosis in two OSCC cell lines. QSAR analysis demonstrated that their tumor-specificity of azulene amide derivatives was correlated with hydrophobicity and molecular shape.

CONCLUSION:

Compound [1] can be considered as a lead compound for manufacturing new anticancer drug candidates.

KEYWORDS:

Azulene amides; apoptosis; cytotoxicity; hydrophobicity; molecular shape; tumor specificity

PMID:
29695549
PMCID:
PMC6000805
DOI:
10.21873/invivo.11264
[Indexed for MEDLINE]
Free PMC Article

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