Are Vanadium Compounds Drugable? Structures and Effects of Antidiabetic Vanadium Compounds: A Critical Review

Scior, Thomas; Guevara-Garcia, Antonio; Bernard, Philippe; Do, Quoc‐Tuan; Domeyer, David; Laufer, Stefan

doi:10.2174/138955705774575264

Cited by 48 publications

(40 citation statements)

References 98 publications

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“…Recently, Scior et al critically reviewed the question of the drugability of vanadium compounds and concluded that vanadium is a drugable agent. It is, however, essential to develop more potent vanadium compounds with higher efficacy and reduced side effects [8]. Vanadium efficacy can be increased by synthesis of organic vanadium chelates.…”

Section: Introductionmentioning

confidence: 99%

Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

Shukla

Padhyé²,

Modak³

et al. 2007

Rev Diabet Stud

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■ AbstractOrganic vanadium compounds offer several advantages in the treatment of diabetes, yet they are impractical to use because of known side effects. In order to ameliorate the side effects of vanadium, we conjugated it with quercetin to form bis(quercetinato)oxovanadium IV (BQOV). This study evaluates the effect of BQOV treatment on carbohydrate metabolism and overall oxidative stress in streptozotocininduced (STZ) diabetic mice. Administration of BQOV orally to diabetic mice for 3 weeks led to a reduction of blood glucose levels and the animals exhibited normal glucose tolerance at the end of the study period. The increase in glucose uptake by skeletal muscle and liver as well as the normalization of mRNA levels of G-6-Pase and glucokinase in the liver after BQOV treatment pointed to improvements in carbohydrate metabolism. The analysis of the antioxidant status of serum, liver and pancreas revealed reduced oxidative stress in BQOV-treated animals compared to untreated diabetic controls. Serum analyses for kidney and liver function showed that BQOV treatment provoked total protection of the kidney and partial protection of the liver from diabetogenic insults. The number of insulin-positive cells and the amount of pancreatic insulin in treated mice (1.2038 ± 0.34 ng/mg tissue) did not account for pancreatic regeneration but suggested an insulin-mimetic action on the part of BQOV. Moreover, administration of BQOV for 3 weeks did not show any visible side-effects. This data indicate that BQOV is a safe and potent agent for diabetes treatment, because it is able to improve carbohydrate metabolism and to reduce overall oxidative stress.

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Section: Introductionmentioning

confidence: 99%

Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

Shukla

Padhyé²,

Modak³

et al. 2007

Rev Diabet Stud

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“…This finding could be interpreted against the hypothesis of prodrug function which cannot be ruled out for the more unstable organic vanadium compounds. 46 With regard to the patented compounds, [77][78][79][80][81] an enhanced pharmacokinetic and dynamic drug profile of TSAG0101 can be expected; due to its experimental complex stability and theoretical binding specificity. In biological assays in rats, TSAG0101 showed insulin-like activity (insulin mimesis), also no pancreatic component could be observed, ie, its blood glucose lowering effect is of extrapancreatic nature.…”

Section: Discussionmentioning

confidence: 99%

“…The former imitates the geometry of a phosphate anion, phosphatomimetic group, 46 whereas the latter is composed of unrelated organic rests (strong chelating groups). To this end, pharmacologically and chemically known molecular fragments (A, B, and Q in Figure 2) were combined to build an imaginary compound using Chem3D of the ChemOffice 5.0 tool box.…”

Section: De Novo Designmentioning

confidence: 99%

“…[41][42][43] In addition, vanadium insulin-mimetic effects are superior to other heavy metals (Cr, Zn, and Cd), 44,45 since vanadium research seeks to strengthen therapeutic benefits over toxicities. 46,47 Especially vanadium seems not to present negative accumulation effects. 48 Our present study also aims at the ongoing discussion on the prodrug role of vanadium coordination compounds (stability against ubiquitous citrate).…”

Section: Introductionmentioning

confidence: 98%

“…48 Our present study also aims at the ongoing discussion on the prodrug role of vanadium coordination compounds (stability against ubiquitous citrate). 46 Different research teams have developed new organic compounds of vanadium to improve the drug properties. In the present work, due to the reported identification of a biomolecular target we could devise a so-called de novo design procedure.…”

Section: Introductionmentioning

confidence: 99%

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Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B

Scior

Guevara-García

Melendez

et al. 2010

DDDT

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Prior to its total synthesis, a new vanadium coordination compound, called TSAG0101, was computationally designed to inhibit the enzyme protein tyrosine phosphatase 1B (PTP1B). The PTP1B acts as a negative regulator of insulin signaling by blocking the active site where phosphate hydrolysis of the insulin receptor takes place. H NMR: 4 broad bands from 7.6 to 8.2 ppm and NH 2 shifted to 8.8 ppm. In aqueous solution, in presence or absence of sodium citrate as a biologically relevant and ubiquitous chelator, TSAG0101 undergoes neither ligand exchange nor reduction of its central vanadium atom during 24 hours. TSAG0101 shows blood glucose lowering effects in rats but it produced no alteration of basal-or glucose-induced insulin secretion on β cells during in vitro tests, all of which excludes a direct mechanism evidencing the extrapancreatic nature of its activity. The lethal dose (LD 50 ) of TSAG0101 was determined in Wistar mice yielding a value of 412 mg/kg. This value is one of the highest among vanadium compounds and classifies it as a mild toxicity agent when compared with literature data. Due to its nonsubstituted, small-sized scaffold design, its remarkable complex stability, and low toxicity; TSAG0101 should be considered as an innovative insulin-mimetic principle with promising properties and, therefore, could become a new lead compound for potential nonpeptide PTP1B inhibitors in antidiabetic drug research. In view of the present work, the inhibitory concentration (IC 50 ) and extended solution stability will be tested.

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Amelioration of Hyperglycemia and Metabolic Syndromes in Type 2 Diabetic KKA^y Mice by Poly(γ‐glutamic acid)oxovanadium(IV) Complex

Karmaker¹,

Saha²,

Yoshikawa³

2007

ChemMedChem

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Recently, we found that poly(gamma-glutamic acid)oxovanadium(IV) complex (VO(gamma-pga)) exhibits a potent antidiabetic activity in streptozotocin (STZ)-induced type 1 diabetic mice. This result prompted us to examine its ability to treat the type 2 diabetic model KKA(y) mice with insulin resistance. We studied the in vivo antidiabetic activity of VO(gamma-pga), compared with that of vanadium(IV) oxide sulfate (VS) as control. Both compounds were orally administered at doses of 5-10 mg (0.1-0.2 mmol) V kg(-1) body mass to the KKA(y) mice for 30 days. VO(gamma-pga) normalized the hyperglycemia within 21 days, whereas VS lowered the blood glucose concentration only by a small degree. In addition, the glucose intolerance, HbA(1c) level, hyperinsulinemia, hypercholesterolemia, and hyperleptinemia were significantly improved in VO(gamma-pga)-treated KKA(y) mice compared with those treated with VS. Based on these observations, VO(gamma-pga) is proposed to be the first orally active oxovanadium(IV)-polymer complex for the efficacious treatment of not only type 2 diabetes but also metabolic syndrome in animals.

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Are Vanadium Compounds Drugable? Structures and Effects of Antidiabetic Vanadium Compounds: A Critical Review

Cited by 48 publications

References 98 publications

Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B

Amelioration of Hyperglycemia and Metabolic Syndromes in Type 2 Diabetic KKA^y Mice by Poly(γ‐glutamic acid)oxovanadium(IV) Complex

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Are Vanadium Compounds Drugable? Structures and Effects of Antidiabetic Vanadium Compounds: A Critical Review

Cited by 48 publications

References 98 publications

Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

Bis(quercetinato)oxovanadium IV Reverses Metabolic Changes in Streptozotocin-Induced Diabetic Mice

Chimeric design, synthesis, and biological assays of a new nonpeptide insulin-mimetic vanadium compound to inhibit protein tyrosine phosphatase 1B

Amelioration of Hyperglycemia and Metabolic Syndromes in Type 2 Diabetic KKAy Mice by Poly(γ‐glutamic acid)oxovanadium(IV) Complex

Contact Info

Product

Resources

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Amelioration of Hyperglycemia and Metabolic Syndromes in Type 2 Diabetic KKA^y Mice by Poly(γ‐glutamic acid)oxovanadium(IV) Complex