Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents

Wenlin Xie; Shimin Xie; Ying Zhou; Xufu Tang; Jian Liu; Wenqian Yang; Minghua Qiu

doi:10.1016/j.ejmech.2014.05.001

Design and synthesis of novel 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives as potential anticancer agents

Eur J Med Chem. 2014 Jun 23:81:22-7. doi: 10.1016/j.ejmech.2014.05.001. Epub 2014 May 4.

Authors

Wenlin Xie¹, Shimin Xie², Ying Zhou³, Xufu Tang³, Jian Liu⁴, Wenqian Yang³, Minghua Qiu³

Affiliations

¹ School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, China; Hunan Provincial University Key Laboratory of QSAR/QSPR, China. Electronic address: xwl2000zsu@163.com.
² Hunan University of Humanities, Science and Technology, Loudi 417000, China.
³ School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China; Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan University of Science and Technology, China; Hunan Provincial University Key Laboratory of QSAR/QSPR, China.
⁴ Shenzhen Hanyu Pharmaceutical Co., Ltd., Shenzhen 518057, China.

PMID: 24819956
DOI: 10.1016/j.ejmech.2014.05.001

Abstract

A series of 5,6-disubstituted pyridine-2,3-dione-3-thiosemicarbazone derivatives(2a-2n) and 5,6-disubstituted pyridine-2,3-dione S-benzyl-3-thiosemicarbazones(3a-3g) were synthesized starting from 2,3-dihydroxypyridine via oxidation-Michael additions, condensations and nucleophilic substitutions. The structures of the compounds were established by IR, (1)H NMR, (13)C NMR, and HRMS. All newly synthesized compounds were screened for their anticancer activity against Breast cancer (MCF-7), Colon cancer (HCT-116) and hepatocellular cancer (BEL7402) cell lines. Bioassay results indicated that most of the prepared compounds exhibited cytotoxicity against various cancer cells in vitro. Some of the compounds exhibited promising antiproliferative activity, which were comparable to the positive control (5-fluorouracil). The structure-activity relationship was discussed.

Keywords: 2,3-Dihydroxypyridine; Anticancer activity; Pyridine-2,3-diones; Thiosemicarbazone.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
HCT116 Cells
Humans
MCF-7 Cells
Molecular Structure
Structure-Activity Relationship
Thiosemicarbazones / chemical synthesis
Thiosemicarbazones / chemistry
Thiosemicarbazones / pharmacology*

Substances

5,6-di(o-methylanilino)pyridine-2,3-dione-3-thiosemicarbazone
Antineoplastic Agents
Thiosemicarbazones