Bio-Oriented Synthesis of Novel (S)-Flurbiprofen Clubbed Hydrazone Schiff’s Bases for Diabetic Management: In Vitro and In Silico Studies

Abstract

A new series of (S)-flurbiprofen derivatives 4a–4p and 5a–5n were synthesized with different aromatic or aliphatic aldehydes and ketones to produce Schiff’s bases and their structures were confirmed through HR-ESI-MS, 1H, and 13C-NMR spectroscopy. The α-glucosidase inhibitory activities of the newly synthesized compounds were scrutinized, in which six compounds 5k, 4h, 5h, 4d, 4b, and 5i showed potent inhibition in the range of 0.93 to 10.26 µM, respectively, whereas fifteen compounds 4c, 4g, 4i, 4j, 4l, 4m, 4o, 4p, 5c, 5d, 5j, 5l, 5m, 5n and 1 exhibited significant inhibitory activity with IC50 in range of = 11.42 to 48.39 µM. In addition, compounds 5g, 5f, 4k, 4n, and 4f displayed moderate-to-low activities. The modes of binding of all the active compounds were determined through the molecular docking approach, which revealed that two residues, specifically Glu277 and His351 are important in the stabilization of the active compounds in the active site of α-glucosidase. Furthermore, these compounds block the active site with high binding energies (−7.51 to −3.36 kcal/mol) thereby inhibiting the function of the enzyme.

Para-Substituted Thiosemicarbazones as Cholinesterase Inhibitors: Synthesis, In Vitro Biological Evaluation, and In Silico Study

“…(17). Yellow powder; yield: 76%; 1 (18) ■ RESULTS AND DISCUSSION Chemistry. To discover various pharmacologically/biologically potent cholinesterase inhibitors, efforts were made to synthesize various novel derivatives of para-substituted benzaldehydes in good to excellent yields through multistep reactions.…”

“…These compounds are also known as azomethine, imines, or anils. − Schiff’s bases are the most important organic compounds with a variety of applications; these compounds are extensively used as catalysts in different organic reactions, as stabilizers, in the polymer industry, as pesticides, and also as dyes . Likewise, these compounds also possess various biological or pharmacological activities, like anti-inflammatory, anti-HIV, antiurease, anticholinesterase, antifungal, antioxidant, and α-glucosidase activities . One more application of imine linkage is in vision chemistry, where the link is formed between the active vitamin B6 (pyridoxal phosphate) and the amino acids for the purpose of transamination. − Imine-containing compounds have the potential to form a defensive coating, which makes the surface safe from corrosion …”

“… 11 Likewise, these compounds also possess various biological or pharmacological activities, like anti-inflammatory, 12 anti-HIV, 13 antiurease, 14 anticholinesterase, 15 antifungal, 16 antioxidant, 17 and α-glucosidase activities. 18 One more application of imine linkage is in vision chemistry, where the link is formed between the active vitamin B6 (pyridoxal phosphate) and the amino acids for the purpose of transamination. 19 − 21 Imine-containing compounds have the potential to form a defensive coating, which makes the surface safe from corrosion.…”

Synthetic Transformation of 2-{2-Fluoro[1,1′-biphenyl]-4-yl} Propanoic Acid into Hydrazide–Hydrazone Derivatives: In Vitro Urease Inhibition and In Silico Study

“…Urease inhibitory activity was performed according to the reported method. − Briefly, 40 μL of phosphate buffers at pH 6.8, 10 μL of the synthesized derivatives, and 10 μL of the enzyme were incubated for 10 min at 37 °C in a 96-well plate. To each well, 40 μL of solutions of the phenol reagent and 40 μL of alkali reagent were added.…”

Structural Characterization and Hypoglycemic Function of Polysaccharides from Cordyceps cicadae

“…Drugs for the treatment of T2DM, such as DPP-4 inhibitors and sulfonylureas (SUS), have certain side effects [ 9 , 10 , 11 ]; therefore, finding effective active substances to prevent hyperglycemia is of utmost importance. Interestingly, these substances can also be derived from natural sources [ 12 , 13 ].…”