title: Development of new zinc dithiosemicarbazone complex for use as oral antidiabetic agent.
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.
authors.affiliation: Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kadowaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Munekane
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Hiromura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kamino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
authors.forename: Shuichi
authors.initials: S
authors.lastname: Enomoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D056831:Coordination Complexes / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D013882:Thiosemicarbazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015032:Zinc / Q000737:chemistry*
chemical_list: D001786:Blood Glucose; D056831:Coordination Complexes; D020738:Leptin; D013882:Thiosemicarbazones; C015848:dithiosemicarbazone; D015032:Zinc