Synthesis of novel (R)-4-fluorophenyl-1H-1,2,3-triazoles: A new class of α-glucosidase inhibitors.

Diabetes is a non-communicable disease, which occurs either due to the lack of insulin or the inability of the human body to recognize it. The recent data indicates an increase in the trend of people diagnosed with Type 2 diabetes mellitus (T2DM). α-Glucosidase inhibitors are known to reduce the impact of carbohydrates on blood glucose level and prevent the digestion of carbohydrates. α-glucosidase inhibitors hold great potential for the treatment of T2DM. In search of better α-glucosidase inhibitors, a series of novel (R)-4-fluorophenyl-1H-1,2,3-triazole derivatives were synthesized (6 and 8a-n) and evaluated for their α-glucosidase inhibitory activity in vitro. All new compounds were characterized by 1H NMR, 13C NMR, 19F NMR, ESI-MS, and where applicable by single crystal X-ray diffraction (8 m). A preliminary structure-activity relationship suggested that the presence of 1H-1,2,3-triazole ring in (R)-4-fluorophenyl-1H-1,2,3-triazole derivatives has remarkable contribution in the overall activity. Molecular docking studies were carried out to investigate the binding mode of compounds within the active site of the α-glucosidase enzyme. Docking results are in complete agreement with the experimental finding. This study unravelled a new class of triazole derivatives with α-glucosidase inhibitory activity.

New α-Glucosidase inhibitors from the resins of Boswellia species with structure-glucosidase activity and molecular docking studies.

Phytochemical investigation of the oleo-gum resins from Boswellia papyrifera afforded one new triterpene, named 3α-hydroxyurs-5:19-diene (1) together with twelve known compounds including eight triterpenoids (2-9), two diterpenoids (10 and 11) and two straight chain alkanes (12 and 13). Similarly ten more known compounds were isolated from the resin of Boswellia sacra including one triterpene (20) and nine boswellic acids (14-19 and 21-23). Herein the compound 2 was first time reporting from natural source along with complete NMR assignment, while compounds 3-11 are known, but reported for the first time from the resin of B. papyrifera. The structure elucidation was done by advance spectroscopic 1D and 2D NMR techniques viz., 1H, 13C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. All compounds were evaluated for their α-glucosidase inhibitory activity and as result eight of them 1, 3, 10, 11, 15, and 17-19 were found significantly active against α-glucosidase with an IC50 value ranging from 15.0 ±â€¯0.84 to 80.3 ±â€¯2.33 µM, while 21 exhibited moderate activity with IC50 of 799.9 ±â€¯4.98 µM. Furthermore, two compounds 24 and 25 were synthesised from 16 and 17 to see the effect of carboxyl group in structural-activity relationship (SAR) study. Compounds 24 and 25 retained good α-glucosidase inhibition as compared to 16 and 17, indicating that carboxylic group play a key role in SAR. In addition, the aforementioned activity of all the active compounds was first time reported for their α-glucosidase inhibition potential. The molecular docking studies showed that all the active compounds well accommodate in the active site of the enzyme. Moreover pharmacokinetic properties of the compounds were predicted in silico, suggesting that the compounds possess drug like properties and excellent ADMET profile.

Synthesis of 1H-1,2,3-triazole derivatives as new α-glucosidase inhibitors and their molecular docking studies.

Inhibition of α-glucosidase is an effective strategy for controlling the post-prandial hyperglycemia in diabetic patients. For the identification of new inhibitors of this enzyme, a series of new (R)-1-(2-(4-bromo-2-methoxyphenoxy) propyl)-4-(4-(trifluoromethyl) phenyl)-1H-1,2,3-triazole derivatives were synthesized (8a-d and 10a-e). The structures were confirmed by NMR, mass spectrometry and, in case of compound 8a, by single crystal X-ray crystallography. The α-glucosidase inhibitory activities were investigated in vitro. Most derivatives exhibited significant inhibitory activity against α-glucosidase enzyme. Their structure-activity relationship and molecular docking studies were performed to elucidate the active pharmacophore against this enzyme. Compound 10b was the most active analogue with IC50 value of 14.2 µM, while compound 6 was found to be the least active having 218.1 µM. A preliminary structure-activity relationship suggested that the presence of 1H-1,2,3-triazole ring in 1H-1,2,3-triazole derivatives is responsible for this activity and can be used as anti-diabetic drugs. The molecular docking studies of all active compounds were performed, in order to understand the mode of binding interaction and the energy of this class of compounds.

A Rare Case of Heterotopic Ossification of the Patella Tendon in an Adolescent Presenting with Tendon Rupture.

Heterotopic ossification is the abnormal formation of mature, lamellar bone in nonosseous tissue such as tendons, ligaments, muscles, and soft tissue. We discuss a rare case of a young adolescent with patellar tendon rupture postheterotopic ossification. A 13-year-old male presented to us with knee pain and inability to extend for 6 weeks following trivial trauma. Preliminary radiological investigations revealed a high riding patella with ossification in the patella tendon. The magnetic resonance scan confirmed the same with patellar tendon disruption and heterogeneous ossification. He underwent surgery with patella tendon repair, augmentation with autograft, and had complete recovery at 6 months' follow-up.

New design of experiment combined with UV-Vis spectroscopy for extraction and estimation of polyphenols from Basil seeds, Red seeds, Sesame seeds and Ajwan seeds.

New experimental designs for the extraction of polyphenols from different seeds including Basil seed, Red seed, Sesame seeds and Ajwan seeds were investigated. Four variables the concentration and volume of methanol and NaOH solutions as well as the temperature and time of extraction were varied to see their effect on total phenol extraction. The temperature was varied in the range from 25°C to 200°C while the time in the range from 30 to 200minutes. Response surface methodology was used to optimize the extraction parameters. The estimation of polyphenols was measured through phenols reduction UV-Vis spectroscopic method of phosphotungstic-phosphomolybdic acids (Folin-Ciocalteu's reagent). Calibration curve was made by using tannic acid as a polyphenols standard in the concentration range from 0.1 to 10ppm. The regression line obtained shows the value of correlation coefficient i.e. R=0.930 and Root mean square error of cross validation (RMSEC) value of 0.0654. The Basil seeds were found containing the highest amount of total phenols i.e. 785.76mg/100g. While the Sesame seeds having the least amount i.e. 33.08mg/100g. The Ajwan seeds and the Red seeds are containing the medium amounts i.e. 379mg/100g and 220.54mg/100g respectively.