Until now, many of the metals have been reported to possess anti-diabetic potential, such as vanadium ( Heyliger et al., 1985), chromium ( Anderson et al., 1997), cobalt ( Ybarra et al., 1997), molybdenum ( Ozcelikay et al., 1996), tungsten ( Barberà et al., 2001), cadmium ( Gümüşlü et al., 1997), iron, and copper ( Siva and Kumar, 2013). Thus, patients with type II diabetes rely on synthetic anti-diabetic therapy ( Nathan et al., 2009). However, type II diabetes is associated with relatively reduced levels or/and reduced sensitivity of hepatic, cardiac and fat cell toward insulin action. Hyperglycemic condition in type I diabetes is controlled by administering exogenous insulin via subcutaneous route. Type I diabetes is associated with deficiency of insulin due to autoimmune-mediated β cells damage ( Tuomi, 2005). DM is mainly characterized by high blood glucose levels, i.e., hyperglycemia with altered metabolism of carbohydrates, proteins and fats due to reduced insulin secretions or/and insulin action. According to WHO, the 7th chief cause of deaths in 2030 will be DM ( Mathers and Loncar, 2006). Factors responsible for DM include increased deskbound lifestyle, nutrition changeover and rapid urbanization leading to widespread, parallel to rise in obesity ( Hu, 2011). These results indicate that aforementioned derivatives of ferrocene and cadmium possess anti-diabetic potential.ĭiabetes mellitus (DM) is foremost health disorder, growing frequently in developing countries. DPAA and DPCI dose-dependently at 1, 5, and 10 mg/Kg decreased glycosylated hemoglobin levels in diabetic animals, as caused by metformin. DPAA (10 mg/Kg) and DPC1 (5 mg/Kg) in time-dependent manner (30–120 min.) enhanced tolerance of oral glucose overload in mice.
In alloxan (300 mg/Kg)-induced diabetic mice, DPAA and DPC1 (1–10 mg/Kg) at day 1, 5, 10, 15, and 20th decreased blood glucose levels, compared to diabetic control group and improved the treated animals body weight. alpha amylase, protein tyrosine phosphatases 1B, glycogen phosphorylase and phosphatidylinositol 3 kinase. PFA, DPC1, DMC1, DOC1, DPAA and CPAA exhibited high binding affinities (ACE ≥ −350 Kcal/mol) against targets: aldose reductase, peroxisome proliferator-activated receptor γ, 11β-hydroxysteroid dehydrogenase-1, C-alpha glucosidase and glucokinase, while showed moderate affinities (ACE ≥ −250 Kcal/mol) against N-alpha glucosidase, dipeptidyl peptidase-IV, phosphorylated-Akt, glycogen synthase kinase-3β, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, whereas revealed lower affinities (ACE < −250 Kcal/mol) vs. We investigated possible anti-diabetic effect of ferrocene-based acyl ureas: 4-ferrocenyl aniline (PFA), 1-(4-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DPC1), 1-(3-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DMC1), 1-(2-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DOC1) and homoleptic cadmium carboxylates: bis (diphenylacetato) cadmium (II) (DPAA), bis (4-chlorophenylacetato) cadmium (II) (CPAA), using in silico and in vivo techniques. 3Department of Chemistry, University of Wah, Wah, Pakistan.2Department of Chemistry, Quaid-e-Azam University, Islamabad, Pakistan.1Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan.
Shahar Bano 1, Arif-ullah Khan 1 *, Faiza Asghar 2,3, Muhammad Usman 2, Amin Badshah 2 and Saqib Ali 2
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