GLP-1 Targeted Novel 3-phenyl-7-hydroxy Substituted Coumarins Mitigate STZ-induced Pancreatic Damage and Improve Glucose Homeostasis in OGTT Method.

BACKGROUND: Worldwide, type 2 diabetes mellitus accounts for a considerable burden of disease, with an estimated global cost of >800 billion USD annually. For this reason, the search for more effective and efficient therapeutic anti-diabetic agents is continuing. Recent studies support the search for coumarins or related compounds with potential blood glucose-lowering properties. AIM: The study aims to design, synthesize and evaluate the hypoglycemic activity of a new class of 7-hydroxy coumarin derivatives. OBJECTIVE: To explore and establish the in-silico-driven pharmacological role of a new class of 7- hydroxy coumarin derivatives as the therapeutic strategies against type 2 diabetes mellitus. METHODS: A new class of 7-hydroxy coumarin derivatives was designed by assessment of their physicochemical properties and molecular docking against the Glucagon-like peptide-1 (GLP-1) receptor. Two novel series of 30 compounds were synthesized. The chemical structures of all the synthesized analogues have been elucidated by spectral studies of IR, 1H-NMR, and mass spectroscopy. After considering the molecular docking score and their physicochemical properties, the compounds were screened out for the evaluation of their hypoglycemic potential. The compounds were investigated for their hypoglycemic activity using a streptozotocin (STZ) induced diabetic model and an oral glucose tolerance test (OGTT) method at different dose levels. RESULTS: The molecular docking studies of synthesized derivatives reveal significant molecular interaction with the various amino acid residues of the GLP-1 receptor. IR spectral analysis revealed a strong band of -NH stretching in the range of 3406.7-3201.61 cm-1 and one strong band for the lactone carbonyl group of the coumarin ring in the range of 1722.0-1703.5 cm-1, confirming the chemical structure of all produced compounds. The synthesized coumarin analogues with the best docking score exhibited remarkable hypoglycemic potential as assessed by the STZ model and the OGTT method. CONCLUSION: Coumarin derivatives explored a good structure-activity relationship (SAR) and produced significant hypoglycemic potential.

Integrated biological and advanced oxidation based treatment of hexamine bearing wastewater: Effect of cow-dung as a co-substrate.

This work examines the treatment of hexamethylenetetramine (HMT) bearing effluent from N, N-dinitroso pentamethylene tetra-mine producing industrial plants in India. Chemical treatment using Fenton's reagent and aerobic treatment using batch reactors with co-substrate were investigated. Aerobic batch reactors integrated with advanced oxidation process of Fenton's reagent provides effective treatment of HMT effluents. Influence of Fenton's reagent dose reaction/contact and effect of varying co-substrate with effluent initial concentration was observed. Higher dose 100 mL of Fenton's reagent with higher reaction time 20 h resulted better degradation (34.88%) of wastewater. HMT hydrolyzes in acidic environment to ammonia and formaldehyde. Formaldehyde under normal conditions is toxic for biological treatment processes. When hydrolysis and acidification in the reactors are accompanied by low pH, aerobic batch reactors with use of co-substrates glucose, sucrose, and cow-dung extract separately in different proportion to wastewater ranging from 0.67 to 4.00, degraded wastewater effectively. Higher proportion of co-substrate to wastewater resulted better degradation. The relationships between nitrate, pH, turbidity and COD are discussed.