In view of the clinical use of vanadium compounds, we prepared seven analogs of a vanadylpicolinate complex (VO(pic)2) with VO(N2O2) coordination mode, which was found in 1995 to exhibit highly effective and long-term insulinomimetic activity in treating both streptozotocin (STZ)-induced type 1 diabetic rats (STZ rats) and hereditarily type 2 diabetic KK-A y mice by daily intraperitoneal (i.p.) injections and on oral administration, to find the structureactivity relationship of the complexes. Using an in vitro insulinomimetic evaluation of the complexes in terms of their inhibiting effect on free fatty acids release from isolated rat adipocytes treated with epinephrine (adrenaline), we found the activity (IC50 :5 0% inhibitor’s concentration of the complex on the free fatty acid release) to be as follows: VO(5ipa)2 > VO(3mpa)2 > VO(6mpa)2 > VO(3hpa)2 > VO(pic)2 > VO(6hpa)2 » VOSO4, indicating that the introduction of an electron-withdrawing halogen atom or an electron-donating methyl group at the 5th or 3rd position on the picolinate ligand causes stronger insulinomimetic activity than that of the lead complex VO(pic)2. Next we examined the pharmacokinetic features in the blood of the complexes by using the blood circulation-monitoring electron spin resonance method, in which good linear relationships between the pharmacokinetic parameters and the IC50 values were found. Based on the results, we tested the complexes and found that both VO(5ipa)2 and VO(3mpa)2 complexes treat type 1 diabetes in STZ rats. Because the daily oral administration of vanadyl complexes is the only method to treat type 1 diabetes in place of daily insulin injections, the present results will be useful for the development of vanadyl complexes with high safety and long-term activity. J. Trace Elem. Exp. Med. 16:269280, 2003. � 2003 Wiley-Liss, Inc.
{"title":"Structure–activity relationship of insulinomimetic vanadyl–picolinate complexes in view of their clinical use","authors":"Hiromu Sakurai, Hiroyuki Yasui","doi":"10.1002/jtra.10036","DOIUrl":"https://doi.org/10.1002/jtra.10036","url":null,"abstract":"In view of the clinical use of vanadium compounds, we prepared seven analogs of a vanadylpicolinate complex (VO(pic)2) with VO(N2O2) coordination mode, which was found in 1995 to exhibit highly effective and long-term insulinomimetic activity in treating both streptozotocin (STZ)-induced type 1 diabetic rats (STZ rats) and hereditarily type 2 diabetic KK-A y mice by daily intraperitoneal (i.p.) injections and on oral administration, to find the structureactivity relationship of the complexes. Using an in vitro insulinomimetic evaluation of the complexes in terms of their inhibiting effect on free fatty acids release from isolated rat adipocytes treated with epinephrine (adrenaline), we found the activity (IC50 :5 0% inhibitor’s concentration of the complex on the free fatty acid release) to be as follows: VO(5ipa)2 > VO(3mpa)2 > VO(6mpa)2 > VO(3hpa)2 > VO(pic)2 > VO(6hpa)2 » VOSO4, indicating that the introduction of an electron-withdrawing halogen atom or an electron-donating methyl group at the 5th or 3rd position on the picolinate ligand causes stronger insulinomimetic activity than that of the lead complex VO(pic)2. Next we examined the pharmacokinetic features in the blood of the complexes by using the blood circulation-monitoring electron spin resonance method, in which good linear relationships between the pharmacokinetic parameters and the IC50 values were found. Based on the results, we tested the complexes and found that both VO(5ipa)2 and VO(3mpa)2 complexes treat type 1 diabetes in STZ rats. Because the daily oral administration of vanadyl complexes is the only method to treat type 1 diabetes in place of daily insulin injections, the present results will be useful for the development of vanadyl complexes with high safety and long-term activity. J. Trace Elem. Exp. Med. 16:269280, 2003. � 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"269-280"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Trace elements in human health and disease: An update","authors":"Ananda S. Prasad","doi":"10.1002/jtra.10057","DOIUrl":"https://doi.org/10.1002/jtra.10057","url":null,"abstract":"","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This review summarizes the evidence for boron essentiality across the biological spectrum with special focus on biochemical pathways and biomolecules relevant to immune function. Boron is an essential trace element for at least some organisms in each of the phylogenetic kingdoms Eubacteria, Stramenopila (brown algae and diatoms), Viridiplantae (green algae and familiar green plants), Fungi, and Animalia. Discovery of several of the currently recognized boron-containing biomolecules was achieved because the bound boron formed four coordinate covalent bonds with the ligand, creating a thermodynamically stable complex that is almost undissociable in water. Boron is a constitutive element in three antibiotics and a quorum-sensing signal in bacteria. It enhances Fc receptor expression and interleukin-6 production in cultured mammalian macrophages. Boron binds tightly to the diadenosine polyphosphates and inhibits the in vitro activities of various serine protease and oxidoreductase enzymes. Physiological amounts of dietary boron decrease skinfold thickness after antigen injection in gilts and elevated circulating natural killer cells after adjuvant injection in rats. It is predicted that several boron biomolecules waiting discovery are signaling molecules that interact with the cell surface and are probably composed of two mirror or near-mirror halves stabilized by a single boron atom to form a large circular bio
{"title":"Dietary boron: An overview of the evidence for its role in immune function†","authors":"Curtiss D. Hunt","doi":"10.1002/jtra.10041","DOIUrl":"https://doi.org/10.1002/jtra.10041","url":null,"abstract":"This review summarizes the evidence for boron essentiality across the biological spectrum with special focus on biochemical pathways and biomolecules relevant to immune function. Boron is an essential trace element for at least some organisms in each of the phylogenetic kingdoms Eubacteria, Stramenopila (brown algae and diatoms), Viridiplantae (green algae and familiar green plants), Fungi, and Animalia. Discovery of several of the currently recognized boron-containing biomolecules was achieved because the bound boron formed four coordinate covalent bonds with the ligand, creating a thermodynamically stable complex that is almost undissociable in water. Boron is a constitutive element in three antibiotics and a quorum-sensing signal in bacteria. It enhances Fc receptor expression and interleukin-6 production in cultured mammalian macrophages. Boron binds tightly to the diadenosine polyphosphates and inhibits the in vitro activities of various serine protease and oxidoreductase enzymes. Physiological amounts of dietary boron decrease skinfold thickness after antigen injection in gilts and elevated circulating natural killer cells after adjuvant injection in rats. It is predicted that several boron biomolecules waiting discovery are signaling molecules that interact with the cell surface and are probably composed of two mirror or near-mirror halves stabilized by a single boron atom to form a large circular bio","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"291-306"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}