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.

Differentiation of stem cells into insulin‐producing cells under the influence of nanostructural polyoxometalates

“…V cytotoxicity is well known and it depends on its degree of oxidation and chemical form (organic or inorganic) (Goc, 2006). Recently, two V (IV and V) compounds were synthesized that showed potent hypoglycemic activities and moderate toxic effects in a rat model (Fedorova et al, 2014). On the other hand, Voroshilin et al (1978) reported a genotoxic dose of 10 μg ml -1 tungstate on human lymphocytes.…”

Ameliorative effect of an oxovanadium (IV) complex against oxidative stress and nephrotoxicity induced by cisplatin

“…Vanadium is an essential trace element that is involved in numerous biological processes in plants, mammals and microorganisms [9]. Vanadium-based compounds exhibit a broad range of pharmacological activities, namely, antioxidant property, anticarcinogenic effect, lowering of cholesterol, triglycerides and glucose levels, diuretic effect, contraction of blood vessels, enhancement of oxygen-affinity of hemoglobin and myoglobin, etc [9,10]. Vanadium also functions as an oxidation-reduction catalyst [11].…”

Vanadium rutin complex sensitizes breast cancer cells via modulation of p53/Bax/Bcl2/VEGF correlated with apoptotic events

“…Vanadium, a transition metal, is a biologically important element incorporated in a number of physiological processes. Vanadium compounds, in particular organic derivatives, are effective in various diseases like diabetes, cancer, hypertension, Ischemia and Myocardial Stroke (45). The formation of a complex between metals and flavonoids plays an important role to forage free radicals as compared to the parent molecule resulting in reduced toxicity of the metals (46).…”