Antitumor Activity of Alkylaminoguaiazulenes

Overview

Journal In Vivo

Specialty Oncology

Date 2018 Apr 27

PMID 29695558

Citations 5

Authors

Mari Uehara

Himawari Minemura

Tsunenori Ohno

Masashi Hashimoto

Hidetsugu Wakabayashi

Noriyuki Okudaira

Hiroshi Sakagami

Affiliations

Soon will be listed here.

Abstract

Background/aim: Guaiazulene (1,4-dimethyl-7-isopropylazulene) is present in several essential oils of medicinal and aromatic plants. There exist few studies that investigated the anticancer activity of guaiazulenes. We investigated the relative cytotoxicity of 10 alkylaminoguaiazulene derivatives towards both cancer and normal cells.

Materials And Methods: Cytotoxicity towards four human oral squamous cell carcinoma (OSCC) cell lines and five types of human normal oral cells (gingival fibroblasts, periodontal ligament fibroblasts, pulp cells and keratinocytes, gingival epithelial progenitors) was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Tumor specificity (TS) was evaluated as the ratio of the mean 50% cytotoxic concentration against normal oral cells to that against OSCC cell lines. Apoptosis-inducing activity was evaluated by cleavage of poly ADP-ribose polymerase and caspsase-3 with western blot analysis.

Results: Validity of the present TS measurement method was confirmed using methotrexate. With increasing length of the alkyl group of alkylaminoguaiazulene derivatives, cytotoxicity increased. Introduction of oxygen, nitrogen or sulfur atom into the alkyl group slightly reduced cytotoxicity. Most compounds had very low TS, no synergistic action with methotrexate and doxorubicin, nor did they induce apoptosis of OSCC cells. On the other hand, compound [], containing a morpholino group, induced apoptosis of OSCC cells.

Conclusion: The cytotoxicity of alkylaminoguaiazulenes is not always coupled with TS and apoptosis-inducing activity.

Citing Articles

Tumor-Specificity, Neurotoxicity, and Possible Involvement of the Nuclear Receptor Response Pathway of 4,6,8-Trimethyl Azulene Amide Derivatives.

Naitoh K, Orihara Y, Sakagami H, Miura T, Satoh K, Amano S Int J Mol Sci. 2022; 23(5).

PMID: 35269748 PMC: 8910578. DOI: 10.3390/ijms23052601.

Guaiazulene Triggers ROS-Induced Apoptosis and Protective Autophagy in Non-small Cell Lung Cancer.

Ye Q, Zhou L, Jin P, Li L, Zheng S, Huang Z Front Pharmacol. 2021; 12:621181.

PMID: 33935713 PMC: 8082441. DOI: 10.3389/fphar.2021.621181.

In vitro and in vivo biological activities of azulene derivatives with potential applications in medicine.

Bakun P, Czarczynska-Goslinska B, Goslinski T, Lijewski S Med Chem Res. 2021; 30(4):834-846.

PMID: 33551629 PMC: 7847300. DOI: 10.1007/s00044-021-02701-0.

Development of Heterocycle-Substituted and Fused Azulenes in the Last Decade (2010-2020).

Shoji T, Okujima T, Ito S Int J Mol Sci. 2020; 21(19).

PMID: 32992955 PMC: 7582284. DOI: 10.3390/ijms21197087.

QSAR Prediction Model to Search for Compounds with Selective Cytotoxicity Against Oral Cell Cancer.

Nagai J, Imamura M, Sakagami H, Uesawa Y Medicines (Basel). 2019; 6(2).

PMID: 30939759 PMC: 6631777. DOI: 10.3390/medicines6020045.

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