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

Autor: Naitoh K; Faculty of Science, Josai University, Saitama 250-0295, Japan., Orihara Y; Faculty of Science, Josai University, Saitama 250-0295, Japan., Sakagami H; Research Institute of Odontology, Meikai University, Sakado, Saitama 350-0283, Japan., Miura T; Faculty of Science, Josai University, Saitama 250-0295, Japan., Satoh K; Division of Pharmacology, Department of Diagnostics and Therapeutics Sciences, Meikai University School of Dentistry, Saitama 350-0283, Japan., Amano S; Research Institute of Odontology, Meikai University, Sakado, Saitama 350-0283, Japan., Bandow K; Division of Biochemistry, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, Saitama 350-0283, Japan., Iijima Y; Department of Oral and Maxillofacial Surgery, Saitama Medical Center, Saitama Medical University, Saitama 350-0283, Japan., Kurosaki K; Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Tokyo 204-8588, Japan., Uesawa Y; Department of Medical Molecular Informatics, Meiji Pharmaceutical University, Tokyo 204-8588, Japan., Hashimoto M; Faculty of Science, Josai University, Saitama 250-0295, Japan., Wakabayashi H; Faculty of Science, Josai University, Saitama 250-0295, Japan.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Feb 26; Vol. 23 (5). Date of Electronic Publication: 2022 Feb 26.
DOI: 10.3390/ijms23052601
Abstrakt: Background: Very few papers covering the anticancer activity of azulenes have been reported, as compared with those of antibacterial and anti-inflammatory activity. This led us to investigate the antitumor potential of fifteen 4,6,8-trimethyl azulene amide derivatives against oral malignant cells.
Methods: 4,6,8-Trimethyl azulene amide derivatives were newly synthesized. Anticancer activity was evaluated by tumor-specificity against four human oral squamous cell carcinoma (OSCC) cell lines over three normal oral cells. Neurotoxicity was evaluated by cytotoxicity against three neuronal cell lines over normal oral cells. Apoptosis induction was evaluated by Western blot and cell cycle analyses.
Results: Among fifteen derivatives, compounds 7 , 9 , and 15 showed the highest anticancer activity, and relatively lower neurotoxicity than doxorubicin, 5-fluorouracil (5-FU), and melphalan. They induced the accumulation of a comparable amount of a subG 1 population, but slightly lower extent of caspase activation, as compared with actinomycin D, used as an apoptosis inducer. The quantitative structure-activity relationship analysis suggests the significant correlation of tumor-specificity with a 3D shape of molecules, and possible involvement of inflammation and hormone receptor response pathways.
Conclusions: Compounds 7 and 15 can be potential candidates of a lead compound for developing novel anticancer drugs.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje