Development of new zinc dithiosemicarbazone complex for use as oral antidiabetic agent

Saori Kadowaki, Masayuki Munekane, Yoji Kitamura, Makoto Hiromura, Shinichiro Kamino, Yutaka Yoshikawa, Hideo Saji, Shuichi Enomoto

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The increasing prevalence of diabetes mellitus (DM) worldwide has underscored the urgency of developing an efficient therapeutic agent. Recently, Zn complexes have been attracting attention due to their antidiabetic activity. In this study, we designed and synthesized a new Zn complex, Zn-3,4-heptanedione-bis(N 4-methylthiosemicarbazonato) (Zn-HTSM), characterized its physicochemical properties, and examined its antidiabetic activity in KK-Ay type 2 DM model mice. It was demonstrated that Zn-HTSM has adequate lipophilicity for the cellular permeability, shows potent hypoglycemic activity, and improves glucose intolerance in KK-Ay mice. We also analyzed the levels of serum adipokines after continuous oral administration of Zn-HTSM. The level of serum leptin of KK-Ay mice is significantly reduced by the treatment of Zn-HTSM. Nevertheless, the levels of serum insulin and adiponectin were not improved. These data suggested that the Zn-HTSM acts on the leptin metabolism. Our present studies indicate that Zn-HTSM is a candidate oral antidiabetic agent for the treatment of type 2 DM.

Original languageEnglish
Pages (from-to)111-119
Number of pages9
JournalBiological Trace Element Research
Volume154
Issue number1
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Glucose intolerance
  • Hypoglycemic activity
  • Leptin resistance
  • Oral antidiabetic agents
  • Zinc dithiosemicarbazone complexes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical
  • Inorganic Chemistry

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  • Cite this

    Kadowaki, S., Munekane, M., Kitamura, Y., Hiromura, M., Kamino, S., Yoshikawa, Y., Saji, H., & Enomoto, S. (2013). Development of new zinc dithiosemicarbazone complex for use as oral antidiabetic agent. Biological Trace Element Research, 154(1), 111-119. https://doi.org/10.1007/s12011-013-9704-x