Mitigating effects of agmatine on myocardial infarction in rats subjected to isoproterenol.

Isoproterenol (ISO) usage is limited by its potential for cardiotoxicity. We sought to investigate the potential of agmatine in mitigating ISO-induced cardiotoxicity. Agmatine (100 mg/kg/day) was intraperitoneally administered to Wistar rats for 7 days in the presence or absence of cardiotoxicity induced by subcutaneous injection of ISO (85 mg/kg) on the sixth and seventh days. ECG parameters, lactate dehydrogenase (LDH), malondialdehyde (MDA), and creatinine phosphokinase (CPK) were investigated. Changes in cardiac tissue were also investigated using H&E staining. The heart weight/body weight ratio increased in ISO-treated rats. In the agmatine + ISO group, the increased heart rate observed in ISO-treated rats was reversed (317.2 ± 10.5 vs 452.2 ± 10.61, P < 0.001). Agmatine ameliorated the change in PR, RR, and ST intervals and the QRS complex, which was reduced by ISO. Treatment with saline, ISO, and agmatine had no significant effect on papillary muscle stimulation (P > 0.05). The administration of agmatine to ISO-receiving group could mitigate several parameters when compared to ISO-receiving group including increasing papillary muscle contraction (0.83 vs 0.71 N/M2 respectively, P < 0.01), decreasing LDH levels (660 ng/ml vs 1080 ng/ml, respectively, P < 0.05), decreasing CPK levels (377 U/l vs 642 U/l, respectively, P < 0.05) and decreasing MDA levels (20.32 µM/l vs 46.83 µM/l, P < 0.001). Coadministration of agmatine and ISO is capable of ameliorating ISO cardiotoxicity by antioxidant effects and controlling the hemostasis of calcium in myocytes.

Fast anisotropic growth of the biomineralized zinc phosphate nanocrystals for a facile and instant construction of laccase@Zn3(PO4)2 hybrid nanoflowers.

Organic-inorganic hybrid nanoflowers (HNFs) of laccase@Zn3(PO4)2 were fabricated through a facile, simple, and rapid one-step strategy. In this process, laccase was involved in nucleation and fast anisotropic growth reactions with Zn (II) and phosphate ions. The average pore size of the prepared HNFs was 54.5 nm, and its BET-specific surface area was 59.5 m2 g-1. In comparison with the free laccase, the entrapped enzyme activity in the constructed HNFs was 86.4%. In addition, the hybrid biocatalyst displayed a maximum rate of reaction (Vmax) of 1640.2 ± 3.6 µmol min-1 with respect to the native enzyme. The constructed HNFs maintained 45.1% and 60% of the original laccase activity after 12 successive reusability cycles and 30 days of storage at 4 °C, respectively. The as-obtained HNFs demonstrated a high bioremoval percentage of Direct blue-71 (94.1%) within a 10-h-treatment at 40 °C and 15 mg l-1 of the dye concentration. The pseudo-first order and second order were the best-fitted kinetic models for the dye removal using Zn3(PO4)2 nanoflakes and the fabricated HNFs, respectively. Besides, liquid chromatography-mass spectrometry (LC-MS) revealed biotransformation of the dye into less toxic metabolites as verified by testing on some bacterial strains.

Novel Coumarin Containing Dithiocarbamate Derivatives as Potent α-Glucosidase Inhibitors for Management of Type 2 Diabetes.

BACKGROUND: α-Glucosidase is a hydrolyzing enzyme that plays a crucial role in the degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in carbohydrate mediated diseases such as diabetes mellitus. OBJECTIVE: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. METHODS: These compounds were obtained from the reaction between 4-(bromomethyl)-7- methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence of potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, a docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). RESULTS: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 µM) in comparison to acarbose as a standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, the secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound competes with a substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Moreover, a molecular docking study predicted that this compound interacted with the α-glucosidase active site pocket. CONCLUSION: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for designing potent α-glucosidase inhibitors for the treatment of type 2 diabetes.

Biscoumarin-1,2,3-triazole hybrids as novel anti-diabetic agents: Design, synthesis, in vitro α-glucosidase inhibition, kinetic, and docking studies.

A novel series of biscoumarin-1,2,3-triazole hybrids 6a-n was prepared and evaluated for α-glucosidase inhibitory potential. All fourteen derivatives exhibited excellent α-glucosidase inhibitory activity with IC50 values ranging between 13.0 ±â€¯1.5 and 75.5 ±â€¯7.0 µM when compared with the acarbose as standard inhibitor (IC50 = 750.0 ±â€¯12.0 µM). Among the synthesized compounds, compounds 6c (IC50 = 13.0 ±â€¯1.5 µM) and 6g (IC50 = 16.4 ±â€¯1.7 µM) exhibited the highest inhibitory activity against α-glucosidase and were non-cytotoxic towards normal fibroblast cells. Kinetic study revealed that compound 6c inhibits the α-glucosidase in a competitive mode. Furthermore, molecular docking investigation was performed to find interaction modes of the biscoumarin-1,2,3-triazole derivatives.