title: Bis(allixinato)oxovanadium(IV) complex is a potent antidiabetic agent: studies on structure-activity relationship for a series of hydroxypyrone-vanadium complexes.
abstract: There is an urgent medical need for orally effective drugs to replace insulin injections for the treatment of diabetes mellitus. Vanadium complexes with insulin-mimetic activities have recently been proposed as candidates as new antidiabetic drugs. Following in vitro and in vivo studies on a group of bis(3-hydroxy-4-pyronato)oxovanadium(IV) (1) complexes with VO(O4) coordination mode, bis(allixinato)oxovanadium(IV) (3) which contains allixin, a garlic component, was found to be the most potent antidiabetic agent among them. Complex 3 with a high in vitro insulin-mimetic activity in terms of both free fatty acid (FFA)-release inhibitory and glucose-uptake enhancing activities in isolated rat adipocytes exhibited a high hypoglycemic effect in type 1 diabetic model mice by both intraperitoneal injections and oral administrations. Complex 3 is thus proposed to be one of the most effective candidates for antidiabetic therapy.
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Adachi
authors.forename: Jiro
authors.initials: J
authors.lastname: Yoshida
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Akira
authors.initials: A
authors.lastname: Katoh
authors.forename: Jitsuya
authors.initials: J
authors.lastname: Takada
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sakurai
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D005230:Fatty Acids, Nonesterified / Q000037:antagonists & inhibitors; D005737:Garlic; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011753:Pyrones / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D014639:Vanadium
chemical_list: D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D011753:Pyrones; C511635:bis(allixinato)oxovanadium(IV); D014639:Vanadium; C070727:allixin