Synthesis of novel C4-benzazole naphthalimide derivatives with potent anti-tumor properties against murine melanoma

Yen-Ta Lu; Tien-Ling Chen; Kuo-Song Chang; Chia-Ming Chang; Tsai-Yin Wei; Jen-Wei Liu; Chih-Ang Hsiao; Tzenge-Lien Shih

doi:10.1016/j.bmc.2016.11.057

Synthesis of novel C4-benzazole naphthalimide derivatives with potent anti-tumor properties against murine melanoma

Bioorg Med Chem. 2017 Jan 15;25(2):789-794. doi: 10.1016/j.bmc.2016.11.057. Epub 2016 Nov 30.

Authors

Yen-Ta Lu¹, Tien-Ling Chen², Kuo-Song Chang³, Chia-Ming Chang⁴, Tsai-Yin Wei⁴, Jen-Wei Liu⁵, Chih-Ang Hsiao⁵, Tzenge-Lien Shih⁶

Affiliations

¹ Chest Division, Medical Department, MacKay Memorial Hospital, Zhongshan Dist., 10449 Taipei, Taiwan.
² Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, MacKay Memorial Hospital, Zhongshan Dist., 10449 Taipei, Taiwan.
³ Department of Emergency Medicine, MacKay Memorial Hospital, Zhongshan Dist., 10449 Taipei, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan.
⁴ Department of Medical Research, MacKay Memorial Hospital, Tamsui Dist., 25173 New Taipei City, Taiwan.
⁵ Department of Chemistry, Tamkang University, Tamsui Dist., 25137 New Taipei City, Taiwan.
⁶ Department of Chemistry, Tamkang University, Tamsui Dist., 25137 New Taipei City, Taiwan. Electronic address: tlshih@mail.tku.edu.tw.

PMID: 27939348
DOI: 10.1016/j.bmc.2016.11.057

Abstract

Novel C4-benzazole naphthalimide derivatives were synthesized and tested in vitro and in vivo as anti-cancer drugs. Among these synthetic molecules, compounds 9 and 10 exhibited cytotoxicity against murine B16F10 melanoma cells. In addition, the above-mentioned compounds significantly suppressed lung tumor metastasis with no visible sign of toxicity.

Keywords: B16F10 cells; Benzazole; MTS assay; Melanoma; Naphthalimide; Topoisomerase II.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA Topoisomerases, Type II / metabolism
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Female
Melanoma / drug therapy*
Melanoma / metabolism
Melanoma / pathology
Mice
Mice, Inbred C57BL
Molecular Structure
Naphthalimides / chemical synthesis
Naphthalimides / chemistry
Naphthalimides / pharmacology*
Structure-Activity Relationship
Topoisomerase II Inhibitors / chemical synthesis
Topoisomerase II Inhibitors / chemistry
Topoisomerase II Inhibitors / pharmacology*

Substances

Antineoplastic Agents
Naphthalimides
Topoisomerase II Inhibitors
DNA Topoisomerases, Type II