Aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamides as potent α-glucosidase inhibitors; molecular dynamics, kinetic and structure-activity relationship studies.

Regarding the important role of α-glucosidase enzyme in the management of type 2 diabetes mellitus, the current study was established to design and synthesize aryl-quinoline-4-carbonyl hydrazone bearing different 2-methoxyphenoxyacetamide (11a-o) and the structure of all derivatives was confirmed through various techniques including IR, 1H-NMR, 13C-NMR and elemental analysis. Next, the α-glucosidase inhibitory potentials of all derivatives were evaluated, and all compounds displayed potent inhibition with IC50 values in the range of 26.0 ± 0.8-459.8 ± 1.5 µM as compared to acarbose used as control, except 11f and 11l. Additionally, in silico-induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the newly synthesized compounds over the active site of α-glucosidase.

Design, synthesis, and molecular docking studies of diphenylquinoxaline-6-carbohydrazide hybrids as potent α-glucosidase inhibitors.

A novel series of diphenylquinoxaline-6-carbohydrazide hybrids 7a-o were rationally designed and synthesized as anti-diabetic agents. All synthesized compounds 7a-o were screened as possible α-glucosidase inhibitors and exhibited good inhibitory activity with IC50 values in the range of 110.6 ± 6.0 to 453.0 ± 4.7 µM in comparison with acarbose as the positive control (750.0 ± 10.5 µM). An exception in this trend came back to a compound 7k with IC50 value > 750 µM. Furthermore, the most potent derivative 7e bearing 3-fluorophenyl moiety was further explored by kinetic studies and showed the competitive type of inhibition. Additionally, the molecular docking of all derivatives was performed to get an insight into the binding mode of these derivatives within the active site of the enzyme. In silico assessments exhibited that 7e was well occupied in the binding pocket of the enzyme through favorable interactions with residues, correlating to the experimental results.

Design and synthesis of phenoxymethybenzoimidazole incorporating different aryl thiazole-triazole acetamide derivatives as α-glycosidase inhibitors.

A novel series of phenoxymethybenzoimidazole derivatives (9a-n) were rationally designed, synthesized, and evaluated for their α-glycosidase inhibitory activity. All tested compounds displayed promising α-glycosidase inhibitory potential with IC50 values in the range of 6.31 to 49.89 µM compared to standard drug acarbose (IC50 = 750.0 ± 10.0 µM). Enzyme kinetic studies on 9c, 9g, and 9m as the most potent compounds revealed that these compounds were uncompetitive inhibitors into α-glycosidase. Docking studies confirmed the important role of benzoimidazole and triazole rings of the synthesized compounds to fit properly into the α-glycosidase active site. This study showed that this scaffold can be considered as a highly potent α-glycosidase inhibitor.

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.

Synthesis and biological evaluation of new benzimidazole-1,2,3-triazole hybrids as potential α-glucosidase inhibitors.

In this study, a series of benzimidazole-1,2,3-triazole hybrids 8a-n as new α-glucosidase inhibitors were designed and synthesized. In vitro α-glucosidase inhibition activity results indicated that all the synthesized compounds (IC50 values ranging from 25.2 ± 0.9 to 176.5 ± 6.7 µM) exhibited more inhibitory activity in comparison to standard drug acarbose (IC50 = 750.0 ± 12.5 µM). Enzyme kinetic study on the most potent compound 8c revealed that this compound was a competitive inhibitor into α-glucosidase. Moreover, the docking study was performed in order to evaluation of interaction modes of the synthesized compounds in the active site of α-glucosidase and to explain structure-activity relationships of the most potent compounds and their corresponding analogs.

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.

A two-year utilization of the pharmacist-operated drug information center in Iran.

OBJECTIVE: To assess and describe the call services delivered by drug and poison information call center (DPIC) of 13-Aban pharmacy, which is closely operated by the Department of Clinical Pharmacy, College of Pharmacy affiliated to Tehran University of Medical Sciences. METHODS: All calls services including counseled and follow-up calls provided by 13-Aban DPIC to health care professionals and public were collected, documented, and evaluated in a 2 years period from July 2010 to June 2012 using the designed software. Data analysis was done by SPSS version 16.0. FINDINGS: Totally 110,310 calls services delivered during a 2 years period. Among healthcare professionals, pharmacists, general physicians, and nurses requested more call services respectively (P = 0.001). DPIC could detect 585 potential cases of adverse drug reactions (ADRs) and 420 cases of major drug-drug interactions (DDIs). CONCLUSION: This study by analyzing and reporting the two-years activities of one of the major DPICs in Iran, showed that DPICs can offer drug consultation for healthcare professional and public as well as detect and prevent ADRs and DDIs, and therefore can promote patients' health regarding drug therapy.