title: An orally active antidiabetic vanadyl complex, bis(1-oxy-2-pyridinethiolato)oxovanadium(IV), with VO(S2O2) coordination mode; in vitro and in vivo evaluations in rats.
abstract: According to Pearson's HSAB (hard and soft acids and bases) rule, the vanadyl ion is classified as a hard acid. However, vanadyl-cysteine methyl ester and dithiocarbamate complexes with VO(S2N2) and VO(S4) coordination modes, respectively, that contain bonds with a combination of hard acid (VO2+) and soft base (sulfur) have been found to form stable complexes and exhibit insulin-mimetic activities in in vitro and in vivo evaluations. Based on such observations, a purple bis(1-oxy-2-pyridinethiolato)oxovanadium(IV) (VO(OPT)) complex with VO(S2O2) coordination mode was prepared and found to have a strong insulin-mimetic activity in in vitro evaluation, which followed in vivo effectiveness on intraperitoneal injection and oral administration. Then, we examined the real-time ESR analysis of vanadyl species in the blood of live rats given VO(OPT) by use of the blood circulation monitoring-ESR method. The clearance of vanadyl species from the blood in terms of half-life (t(1/2)) was determined as 15 min in VO(OPT)-treated rats, while t(1/2) of VOSO4-treated rats was 5 min, indicating the long-term acting character of VO(OPT). On the basis of the results, VO(OPT) with VO(S2O2) coordination mode is proposed to be a potent orally active insulin-mimetic complex in treating insulin-dependent diabetes mellitus in experimental animals.
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Japan. sakurai@mb.kyoto-phu.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Sakurai
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: T
authors.initials: T
authors.lastname: Takino
authors.forename: H
authors.initials: H
authors.lastname: Yasui
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004578:Electron Spin Resonance Spectroscopy; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D007275:Injections, Intravenous; D007328:Insulin / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D014638:Vanadates