{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:05:39Z","timestamp":1792188339514,"version":"4.4.0"},"reference-count":58,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006261","name":"Taif University","doi-asserted-by":"publisher","award":["2020\/21"],"award-info":[{"award-number":["2020\/21"]}],"id":[{"id":"10.13039\/501100006261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Magnesium(II), calcium(II), chromium(III), zinc(II), copper(II), and selenium(IV) sitagliptin (STG) complexes\u2014with the general formulas [Mg(STG)2(Cl)2]\u00b76H2O, [Ca(STG)2(Cl)2], [Cr(STG)2(Cl)2]Cl.6H2O, [Zn(STG)2(Cl)2], [Cu(STG)2(Cl)2]\u00b72H2O, and [Se(STG)2(Cl)2]Cl2, respectively\u2014were designed and synthesized by the chemical reactions between metal(II, III, and IV) chloride salts with an STG ligand in situ methanol solvent in a 1:2 stoichiometric ratio (metal:ligand). Tentative structures of the complexes were proposed based on elemental analysis, molar conductance, magnetic moments, thermogravimetric analysis, and spectral (infrared, electronic, and 1H NMR) data. The particle size and morphological investigation were checked on the bases of scanning electron microscopy, transmission electron microscopy, and X-ray powder diffraction analyses. All the Mg2+, Ca2+, Cr3+, Zn2+, Cu2+, and Se4+ complexes were found to be six-coordinated, wherein the STG ligands act as bidentate chelating agents. This study demonstrates that pancreatic tissues are affected by the induction of experimental diabetes mellitus and clarifies the potential of the synthesized STG complexes, which was found to more significantly improve insulin secretion and the pancreatic and glycometabolic complications of diabetic rats than STG alone.<\/jats:p>","DOI":"10.3390\/ijerph18158030","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T10:47:46Z","timestamp":1627555666000},"page":"8030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["In Situ Neutral System Synthesis, Spectroscopic, and Biological Interpretations of Magnesium(II), Calcium(II), Chromium(III), Zinc(II), Copper(II) and Selenium(IV) Sitagliptin Complexes"],"prefix":"10.3390","volume":"18","author":[{"given":"Samy M.","family":"El-Megharbel","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5602-5096","authenticated-orcid":false,"given":"Moamen S.","family":"Refat","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawziah A.","family":"Al-Salmi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reham Z.","family":"Hamza","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","unstructured":"Kessissoglou, D.P. (1995). The Role of Metal Ions in Biological Systems and Medicine. Bioinorganic Chemistry, Springer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1016\/j.ejmech.2010.03.040","article-title":"Identification of a new anti-diabetic agent by combining VOSO4 and vitamin E In a single molecule: Studies on its spectral, thermal and pharmacological properties","volume":"45","author":"Refat","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.molliq.2017.09.005","article-title":"Synthesis of new drug model has an effective antimicrobial and antitumors by combination of cephalosporin antibiotic drug with silver(I) ion in nano scale range: Chemical, physical and biological studies","volume":"244C","author":"Refat","year":"2017","journal-title":"J. Mol. Liq."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.4155\/fmc-2018-0008","article-title":"Synthesis and speculated of new gold(III) melatonin nanometric complex structure: Drug model for testicular protection","volume":"10","author":"Hamza","year":"2018","journal-title":"Future Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e5458","DOI":"10.1002\/aoc.5458","article-title":"Hypolipidemic and hepatoprotective synergistic effects of selenium nanoparticles and vitamin. E against acrylamide-induced hepatic alterations in male albino mice","volume":"34","author":"Hamza","year":"2020","journal-title":"Appl. Organomet. Chem."},{"key":"ref_6","first-page":"534","article-title":"Preparation, spectroscopic, thermal, antihepatotoxicity, hematological parameters and liver antioxidant capacity characterizations of Cd(II), Hg(II), and Pb(II) mononuclear complexes of paracetamol anti-inflammatory drug","volume":"131C","author":"Hamza","year":"2014","journal-title":"Spectrochim. Acta Part A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.cbi.2014.06.024","article-title":"Synthesis, chemical identification and immunological evaluation studies of a novel silver(I) carbocysteine complex","volume":"220","author":"Hamza","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.saa.2014.07.074","article-title":"Synthesis, spectroscopic and thermal characterizations of vanadyl (II) adenine complex prospective as antidiabetic drug agent","volume":"135","author":"Hamza","year":"2015","journal-title":"Spectrochim. Acta Part A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.saa.2014.07.101","article-title":"Synthesis, spectroscopic and thermal studies of Mg(II), Ca(II), Sr(II) and Ba(II) diclofenac sodium complexes as anti-inflammatory drug and their protective effects on renal functions impairment and oxidative stress","volume":"135","author":"Hamza","year":"2015","journal-title":"Spectrochim. Acta Part A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.saa.2016.08.053","article-title":"Spectroscopic, structural characterizations and antioxidant capacity of the chromium(III) niacinamide compound as a diabetes mellitus drug mode","volume":"173C","author":"Refat","year":"2017","journal-title":"Spectrochim. Acta Part A"},{"key":"ref_11","unstructured":"Anastassopoulou, J., Collery, P., Etienne, J.-C., and Theophanides, T. (1992). Metal Ions in Biology and Medicine, John Libbey Eurotext."},{"key":"ref_12","first-page":"3257","article-title":"Nucleic acids and metals I. Chromium, manganese, nickel, iron, and other metals in ribonucleic acid from diverse biological sources","volume":"234","author":"Waker","year":"1959","journal-title":"J.Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.regpep.2010.08.007","article-title":"Sitagliptin protects renal ischemia reperfusion induced renal damage in diabetes","volume":"166","author":"Vaghasiya","year":"2011","journal-title":"Regul. Pept."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1210\/jc.2012-1544","article-title":"Paresh Dandona Sitagliptin exerts an antinflammatory action","volume":"97","author":"Makdissi","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_15","first-page":"789","article-title":"Determination of chemical stability of sitagliptin by LC-UV, LC-MS and FT-IR methods","volume":"164","author":"Gumieniczeka","year":"2019","journal-title":"Analysis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.3389\/fphys.2018.01857","article-title":"Therapeutic options targeting oxidative stress, mitochondrial dysfunction and inflammation to hinder the progression of vascular complications of diabetes","volume":"9","author":"Teodoro","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sakura, H., Hashimoto, N., Sasamoto, K., Ohashi, H., Hasumi, S., Ujihara, N., Kasahara, T., Tomonaga, O., Nunome, H., and Honda, M. (2016). E_ect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: The JAMP study. BMC Endocr. Disord., 16.","DOI":"10.1186\/s12902-016-0149-z"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"164","DOI":"10.2337\/dc15-2780","article-title":"Pancreatic safety of sitagliptin in the TECOS study","volume":"40","author":"Buse","year":"2017","journal-title":"Diabetes Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E253","DOI":"10.1152\/ajpendo.00182.2012","article-title":"The e_ects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF rats: A quantitative and qualitative analysis revealing no evidence of drug-induced pancreatitis","volume":"303","author":"Vrang","year":"2012","journal-title":"AJP Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e4892","DOI":"10.1002\/aoc.4892","article-title":"Synthesis of new antidiabetic agent by complexity between vanadyl (II) sulfate and vitamin B1: Structural, characterization, anti-DNA damage, structural alterations and antioxidative damage studies","volume":"33","author":"Hamza","year":"2019","journal-title":"Appl. Organomet. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/0471141755.ph0547s70","article-title":"Streptozotocin-induced diabetic models in mice and rats","volume":"70","author":"Furman","year":"2015","journal-title":"Curr. Protoc. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Shawky, L.M., Morsi, A.A., el Bana, E., and Hanafy, S.M. (2020). The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin. Biology, 9.","DOI":"10.3390\/biology9010006"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"J. Anal. Biochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0021-9258(19)50881-X","article-title":"A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase","volume":"195","author":"Beers","year":"1952","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.molstruc.2006.12.006","article-title":"Complexes of uranyl (II), vanadyl (II) and zirconyl (II) with orotic acid \u201cvitamin B13\u201d: Synthesis, spectroscopic, thermal studies and antibacterial activity","volume":"842","author":"Refat","year":"2007","journal-title":"J. Mol. Struct."},{"key":"ref_27","unstructured":"Lever, A.B.P. (1968). Inorganic Electronic Spectroscopy, Elsevier."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1021\/ic50098a031","article-title":"Far-infrared and electronic spectra of some bis (ethylenediamine) and related complexes of copper (II) and the relevance of these data to tetragonal distortion and bond strengths","volume":"10","author":"Lever","year":"1971","journal-title":"Inorg. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1021\/ic50005a032","article-title":"Spectrochemical studies of a series of amides as ligands with nickel (II) and chromium (III)","volume":"2","author":"Drago","year":"1963","journal-title":"Inorg. Chem."},{"key":"ref_30","unstructured":"Nakamoto, K. (1978). Infrared and Raman Spectra of Inorganic and Coordination Compounds, Wiely."},{"key":"ref_31","unstructured":"Vein, D.L., Colthup, N.B., Fateley, W.G., and Grasselli, J.G. (1991). The Handbook of Infrared and Raman Characteristic Frequencies of Organic Molecules, Academic Press."},{"key":"ref_32","unstructured":"Silverstein, R.M., Besslor, G.C., and Morrni, D.T.C. (1981). Spectrometric Identification of Organic Compounds, Wiley. [4th ed.]."},{"key":"ref_33","unstructured":"Cullity, B.D. (1978). Elements of X-ray Diffraction, Addision-Wesley Publishing Company. [2nd ed.]."},{"key":"ref_34","first-page":"149","article-title":"Sitagliptin-induced pancreatitis\u2014A longer road than expected.Clin","volume":"2","author":"Nelson","year":"2014","journal-title":"Case Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1159\/000448043","article-title":"Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress","volume":"98","author":"Kelany","year":"2016","journal-title":"Pharmacology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s12020-013-0032-x","article-title":"Zinc and insulin in pancreatic beta-cells","volume":"45","author":"Yang","year":"2014","journal-title":"Endocrine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.taap.2014.01.021","article-title":"High fat diet and GLP-1 drugs induce pancreatic injury in mice","volume":"276","author":"Rouse","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hamza, R.Z., Al-Motaani, S.E., and Al-Talhi, T. (2021). Therapeutic and Ameliorative Effects of Active Compounds of Combretum Molle in the Treatment and Relief from Wounds in a Diabetes Mellitus Experimental Model. Coatings, 11.","DOI":"10.3390\/coatings11030324"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.jvs.2013.04.048","article-title":"Orally administered dipeptidyl peptidase-4 inhibitor (alogliptin) prevents abdominal aortic aneurysm formation through an antioxidant effect in rats","volume":"59","author":"Bao","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, C., Shao, M., Yang, H., Chen, L., Yu, L., Cong, W., Tian, H., Zhang, F., Cheng, P., and Jin, L. (2013). Attenuation of Hyperlipidemia- and Diabetes-Induced Early-Stage Apoptosis and Late-Stage Renal Dysfunction via Administration of Fibroblast Growth Factor-21 Is Associated with Suppression of Renal Inflammation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082275"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nm.4350","article-title":"Insulin action and resistance in obesity and type 2 diabetes","volume":"23","author":"Czech","year":"2017","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/dom.12729","article-title":"Mechanisms of \u03b2-cell functional adaptation to changes in workload","volume":"18","author":"Wortham","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Bonora, E., and DeFronzo, R.A. (2018). Pathogenesis of type 2 diabetes mellitus. Diabetes Epidemiology, Genetics, Pathogenesis, Diagnosis, Prevention, and Treatment, Springer.","DOI":"10.1007\/978-3-319-27317-4"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/jdi.12235","article-title":"Modeling type 2 diabetes in rats using high fat diet and streptozotocin","volume":"5","year":"2014","journal-title":"J. Diabetes Investig."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"483","DOI":"10.3923\/ijp.2016.483.495","article-title":"Potential Ameliorative Effects of Selenium and Chromium Supplementation Against Toxicity and Oxidative Stress in Streptozotocin Diabetic Rats","volume":"12","author":"Hamza","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1021\/cr980432g","article-title":"Functional mimics of superoxide dismutase enzymes as therapeutic agents","volume":"99","author":"Riley","year":"1999","journal-title":"Chem. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.toxrep.2020.01.012","article-title":"Testicular protective and antioxidant effects of selenium nanoparticles on Monosodium glutamate-induced testicular structure alterations in male mice","volume":"7","author":"Hamza","year":"2020","journal-title":"Toxicol. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Al-Baqami, N.M., and Hamza, R.Z. (2021). Protective Effect of Resveratrol against Hepatotoxicity of Cadmium in Male Rats: Antioxidant and Histopathological Approaches. Coatings, 11.","DOI":"10.3390\/coatings11050594"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4469","DOI":"10.1002\/1521-3773(20001215)39:24<4469::AID-ANIE4469>3.0.CO;2-9","article-title":"The Pharmaceutical Potential of Manganese-Based Superoxide Dismutase Mimics","volume":"39","author":"Kramer","year":"2000","journal-title":"Angew Chem. Int. Ed."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.ijbiomac.2018.08.089","article-title":"A manganese-salen complex as dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes","volume":"120","author":"Zhu","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.neuropharm.2009.06.013","article-title":"Tocotrienol attenuates oxidative-nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy","volume":"57","author":"Kuhad","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1159\/000339028","article-title":"Renal and cardiac effects of DPP4 inhibitors\u2014From preclinical development to clinical research","volume":"36","author":"Hocher","year":"2012","journal-title":"Kidney Blood Press Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1111\/j.1476-5381.2012.01971.x","article-title":"Neuroprotective and neurotrophic actions of glucagon- like peptide-1: An emerging opportunity to treat neurodegenerative and cerebrovascular disorders","volume":"166","author":"Salcedo","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.dsx.2014.04.029","article-title":"Recent advances in understanding the role of oxidative stress in diabetic neuropathy","volume":"9","author":"Shakeel","year":"2015","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1177\/0960327120943267","article-title":"Synergistic antioxidant capacities of vanillin and chitosan nanoparticles against reactive oxygen species, hepatotoxicity, and genotoxicity induced by aging in male Wistar rats","volume":"40","author":"Hamza","year":"2021","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"650","DOI":"10.2337\/diacare.29.03.06.dc05-1961","article-title":"Vitamin D and Calcium Intake in Relation to Type 2 Diabetes in Women","volume":"29","author":"Pittas","year":"2006","journal-title":"Diabetes Care"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/BF01318699","article-title":"Chromium deficiency after long-term total parenteral nutrition","volume":"31","author":"Brown","year":"1986","journal-title":"Dig. Dis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3321","DOI":"10.2147\/DDDT.S222127","article-title":"Effects of quercetin, sitagliptin alone or in combination in testicular toxicity induced by doxorubicin in rats","volume":"13","author":"Ahmed","year":"2019","journal-title":"Drug Des. Dev. Ther."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/15\/8030\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:36:42Z","timestamp":1760164602000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/18\/15\/8030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,29]]},"references-count":58,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["ijerph18158030"],"URL":"https:\/\/doi.org\/10.3390\/ijerph18158030","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,29]]}}}