Thompson Katherine H, Liboiron Barry D, Sun Yan, Bellman Karycia D D, Setyawati Ika A, Patrick Brian O, Karunaratne Veranja, Rawji Gulnar, Wheeler Jeffrey, Sutton Kymberley, Bhanot Sanjay, Cassidy Carrie, McNeill John H, Yuen Violet G, Orvig Chris
Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada,
J Biol Inorg Chem. 2003 Jan;8(1-2):66-74. doi: 10.1007/s00775-002-0388-5. Epub 2002 Sep 12.
A series of 2-alkyl-3-hydroxy-4-pyrone oxovanadium(IV) compounds has been synthesized, characterized, and tested for bioactivity as potential insulin-enhancing agents. The vanadyl complexes, bis(maltolato)oxovanadium(IV), BMOV, bis(ethylmaltolato)oxovanadium(IV), BEOV, and bis(isopropylmaltolato)oxovanadium(IV), BIOV, were compared against vanadyl sulfate for glucose-lowering ability, when administered i.p. to STZ-diabetic rats, at a one-time dose of 0.1 mmol kg(-1)body weight. Blood levels of vanadium were determined at regular intervals, to 72 h, following i.p. injection. All complexes tested exceeded vanadyl sulfate in glucose-lowering ability; this effect was not correlated, however, with blood vanadium levels. Analysis of the pharmacokinetics of the disappearance of [ethyl-1-(14)C]BEOV after an oral gavage dose (50 mg kg(-1), 0.144 mmol kg(-1), in a 10 mL kg(-1) volume of 1% CMC solution) indicated clearly that metal ion-ligand dissociation took place relatively soon after oral ingestion of the complex. Half-lives of fast phase uptake and slow phase disappearance for (14)C and V were calculated from a two-compartment model for whole blood, plasma, liver, kidney, bone, small intestine, and lung, ranging from 17 min ( t(1/2)alpha for (14)C, liver) to 30 days ( t(1/2)beta for V, bone). Curves of disappearance of plasma and whole blood (14)C and V diverged dramatically within the first hour after administration of the vanadium complex.
已合成、表征了一系列2-烷基-3-羟基-4-吡喃酮氧钒（IV）化合物，并作为潜在的胰岛素增强剂进行了生物活性测试。将钒氧基配合物双（麦芽醇根）氧钒（IV）、BMOV、双（乙基麦芽醇根）氧钒（IV）、BEOV和双（异丙基麦芽醇根）氧钒（IV）、BIOV，与硫酸氧钒进行比较，以评估其对链脲佐菌素诱导的糖尿病大鼠腹腔注射一次性剂量为0.1 mmol kg⁻¹体重时的降血糖能力。腹腔注射后，定期测定钒的血药浓度，直至72小时。所有测试的配合物在降血糖能力方面均超过硫酸氧钒；然而，这种效果与血钒水平无关。对口服灌胃剂量（50 mg kg⁻¹，0.144 mmol kg⁻¹，溶于10 mL kg⁻¹的1%羧甲基纤维素溶液中）后[乙基-1-¹⁴C]BEOV消失的药代动力学分析清楚地表明，口服摄入配合物后，金属离子-配体相对较快地发生解离。根据全血、血浆、肝脏、肾脏、骨骼、小肠和肺的二室模型计算了¹⁴C和V的快速摄取相和缓慢消除相的半衰期，范围从17分钟（¹⁴C在肝脏中的t₁/₂α）到30天（V在骨骼中的t₁/₂β）。在给予钒配合物后的第一小时内，血浆和全血中¹⁴C和V的消除曲线显著分开。
