Synthesis, Characterization and Hypoglycemic Activity of Zn(II), Cd(II) and Hg(II) Complexes with Glibenclamide

Abstract

Inorganic elements play crucial roles in biological and biomedical processes, and it is evident that many organic compounds used in medicine do not have a purely organic mode of action; some are activated or biotransformed by metal ions including metalloenzymes, others have a direct or indirect effect on metal ion metabolism.1,2) Metals like chromium, zinc, vanadium, copper, selenium, etc., have been reported in lowering the blood sugar level (Hypoglycemia). At the molecular and cellular level, zinc is intimately involved in insulin synthesis, secretion and signalling, and thus, the consequent actions of insulin on metabolism.3,4) In addition to antiviral, antibacterial, antifungal and anticancer properties, 5) various clinical and epidemiological studies suggest that reduced Zn status is associated with diabetes.3,4,6,7) Moreover, zinc is known to be essential for the function and/or structure of several enzymes e.g.; dehydrogenases, aldolases, peptidases, phosphatases, an isomerase, a transphosphorylase, aspartate transcarbamylase, pancreatic carboxpeptidase, and tryptophan desmolase. 8) Zinc-dependent metalloenzymes are also found among oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. 9)Sulfonylureas have received much attention because of their pharmacological activities in the treatment of non-insuline dependent diabetes mellitus (NIDDM) to enhance the sensitivity of tissues to insulin and to stimulate the pancreas to secrete more insulin and comprise the largest group of oral hypoglycemic agents. These are structurally dissimilar, differing primarily with respect to the substituent R at para position of the benzene ring and the group attached to the terminal urea nitrogen RЈ (1). Inspite of side effects like hypoglycemia, central nervous system problems and skin reactions, [10][11][12] glibenclamide, a second generation sulfonylurea drug, is being used widely due to its safe administration with other drugs, low production of diuresis, no significant antidiuretic effect, no or low disulfiran like reaction as well as dual route of excretion without effecting glucose tolerance. [13][14][15][16] It is found that complexes of some active drugs are more effective than the ligand themselves. [17][18][19][20][21] It is the reason that transition metal complexes of established drugs are gaining much biological significance. [22][23][24] The chemistry of sulphonylureas and their metal complexes have created great interest and enthusiasm among the chemists because of their pharmacological importance. Some studies on the coordination chemistry of sulphonylurea drug with Zn 2ϩ , Cd 2ϩ and Hg 2ϩ metals ions have been carried out which is an attempt to examine the mode of action and drug delivery. 25,26) Keeping in view the concept of coordination of suitable metals as central atom, the biologically active compounds often become more effective than desirable drugs. 27) Hence, the objective of this study was to synthesize a metal based drug after long term clinical studies establishing safety (la...

Morphological and Physicochemical Evaluation of Two Distinct Glibenclamide/Hypromellose Amorphous Nanoparticles Prepared by the Antisolvent Method

“…The composition of nano-A and nano-B was determined by solution-state NMR spectroscopy by dissolving the samples in DMSO- d 6 Figures and S4 show the enlarged (3.40–3.60 ppm) and full solution-state 1 H NMR spectra, respectively.…”