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

doi:10.1007/s12011-013-9704-x

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 journal › Article › peer-review

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-A^y 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-A^y mice. We also analyzed the levels of serum adipokines after continuous oral administration of Zn-HTSM. The level of serum leptin of KK-A^y 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 language	English
Pages (from-to)	111-119
Number of pages	9
Journal	Biological Trace Element Research
Volume	154
Issue number	1
DOIs	https://doi.org/10.1007/s12011-013-9704-x
Publication status	Published - 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
Inorganic Chemistry
Biochemistry, medical

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s12011-013-9704-x

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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.",

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

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AU - Kamino, Shinichiro

AU - Yoshikawa, Yutaka

AU - Saji, Hideo

AU - Enomoto, Shuichi

PY - 2013/7

Y1 - 2013/7

N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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