title: Challenge of studies on the development of new Zn complexes (Zn(opt)₂) to treat diabetes mellitus.
abstract: The number of worldwide patients suffering from diabetes mellitus (DM) is forecasted to increase over time. The development of compounds without severe side effects for type 2 DM is required not only to treat DM but also to improve the quality of life (QOL) of patients. In this paper, we have described the synthesis of novel first transition metal complexes with S2O2 coordination mode and discussed their anti-diabetic activities. Di(1-oxy-2-pyridinethiolato)Zn complex (Zn(opt)2) with Zn(S2O2) coordination mode displayed higher insulin mimetic with anti-diabetic activity, compared to the ZnCl2 or clinically used medicine (pioglitazone). In addition, Zn(opt)2 improved the insulin and adiponectine levels in the plasma. The gastrointestinal absorption of the Zn complex was found to be higher than that of ZnCl(2). Based on these results, we propose that the Zn(opt)2 complex with Zn(S2O2) coordination mode is a novel candidate for the treatment of type 2 DM; through oral administration.
authors.affiliation: Kyoto Pharmaceutical University, 5 Nakauti-cho, Misasagi, Yamashina-ku, Kyoto, Japan. yutaka@mb.kyoto-phu.ac.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Akito
authors.initials: A
authors.lastname: Murayama
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Adachi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sakurai
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000031:analogs & derivatives; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D015032:Zinc / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D009942:Organometallic Compounds; D015032:Zinc