title: Design, synthesis and pharmacological evaluation of novel vanadium-containing complexes as antidiabetic agents.
abstract: Based on the data about structure and antidiabetic activity of twenty seven vanadium and zinc coordination complexes collected from literature we developed QSAR models using the GUSAR program. These QSAR models were applied to 10 novel vanadium coordination complexes designed in silico in order to predict their hypoglycemic action. The five most promising substances with predicted potent hypoglycemic action were selected for chemical synthesis and pharmacological evaluation. The selected coordination vanadium complexes were synthesized and tested in vitro and in vivo for their hypoglycemic activities and acute rat toxicity. Estimation of acute rat toxicity of these five vanadium complexes was performed using a freely available web-resource (http://way2drug.com/GUSAR/acutoxpredict.html). It has shown that the selected compounds belong to the class of moderate toxic pharmaceutical agents, according to the scale of Hodge and Sterner. Comparison with the predicted data has demonstrated a reasonable correspondence between the experimental and predicted values of hypoglycemic activity and toxicity. Bis{tert-butyl[amino(imino)methyl]carbamato}oxovanadium (IV) and sodium(2,2'-Bipyridyl)oxo-diperoxovanadate(V) octahydrate were identified as the most potent hypoglycemic agents among the synthesized compounds.
authors: Saint-Petersburg State Chemical Pharmaceutical Academy, Ministry of Healthcare and Social Development of Russian Federation, Saint-Petersburg, Russian Federation.
authors: Elena V
authors: EV
authors: Fedorova
authors: Saint-Petersburg State Chemical Pharmaceutical Academy, Ministry of Healthcare and Social Development of Russian Federation, Saint-Petersburg, Russian Federation.
authors: Anna V
authors: AV
authors: Buryakina
authors: National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America; Orekhovich Institute of Biomedical Chemistry of Russian Academy of Medical Sciences, Moscow, Russian Federation.
authors: Alexey V
authors: AV
authors: Zakharov
authors: Orekhovich Institute of Biomedical Chemistry of Russian Academy of Medical Sciences, Moscow, Russian Federation.
authors: Dmitry A
authors: DA
authors: Filimonov
authors: Orekhovich Institute of Biomedical Chemistry of Russian Academy of Medical Sciences, Moscow, Russian Federation.
authors: Alexey A
authors: AA
authors: Lagunin
authors: Orekhovich Institute of Biomedical Chemistry of Russian Academy of Medical Sciences, Moscow, Russian Federation.
authors: Vladimir V
authors: VV
authors: Poroikov
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004837:Epinephrine; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D015394:Molecular Structure; D061251:Primary Cell Culture; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017208:Rats, Wistar; D014639:Vanadium / Q000737:chemistry*
chemical_list: C000596952:(2,2'-bipyridyl)oxodiperoxovanadate(V); D056831:Coordination Complexes; D007004:Hypoglycemic Agents; C000596951:bis(tert-butyl(amino(imino)methyl)carbamato)oxovanadium(IV); D014639:Vanadium; D004837:Epinephrine