Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents
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 p...
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| Format: | Online |
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Public Library of Science
2014
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109918/ |
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pubmed-41099182014-07-29 Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents Fedorova, Elena V. Buryakina, Anna V. Zakharov, Alexey V. Filimonov, Dmitry A. Lagunin, Alexey A. Poroikov, Vladimir V. Research Article 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. Public Library of Science 2014-07-24 /pmc/articles/PMC4109918/ /pubmed/25057899 http://dx.doi.org/10.1371/journal.pone.0100386 Text en © 2014 Fedorova et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Fedorova, Elena V. Buryakina, Anna V. Zakharov, Alexey V. Filimonov, Dmitry A. Lagunin, Alexey A. Poroikov, Vladimir V. |
| spellingShingle |
Fedorova, Elena V. Buryakina, Anna V. Zakharov, Alexey V. Filimonov, Dmitry A. Lagunin, Alexey A. Poroikov, Vladimir V. Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents |
| author_facet |
Fedorova, Elena V. Buryakina, Anna V. Zakharov, Alexey V. Filimonov, Dmitry A. Lagunin, Alexey A. Poroikov, Vladimir V. |
| author_sort |
Fedorova, Elena V. |
| title |
Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents |
| title_short |
Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents |
| title_full |
Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents |
| title_fullStr |
Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents |
| title_full_unstemmed |
Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents |
| title_sort |
design, synthesis and pharmacological evaluation of novel vanadium-containing complexes as antidiabetic agents |
| description |
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. |
| publisher |
Public Library of Science |
| publishDate |
2014 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4109918/ |
| _version_ |
1613117624720293888 |