Microwave‐assisted synthesis of triazole derivatives conjugated with piperidine as new anti‐enzymatic agents

Abstract

The current study was aimed for the study of piperidine‐based triazole compounds for their biological potential against various enzymes. A novel library of compounds, 9a‐r, having piperidine, 1,2,4‐triazole, and propanamides was synthesized through consecutive steps including the formation of sulfonamide, hydrazide, 1,2,4‐triazole, and thio‐ether. Initially, 4‐methoxybenzenesulfonyl chloride (1) and ethyl isonipecotate (2) were utilized to develop ethyl 1‐(4‐methoxyphenylsulfonyl)‐4‐piperidinecarboxylate (3). The product 3 was converted into respective hydrazide (4) which was further cyclized into 1,2,4‐triazole (5) nucleus. A series of propanamides, 8a‐r, were synthesized from different amines, 6a‐r. These electrophiles, 8a‐r, were reacted with compound 5 under conventional and microwave‐assisted protocols to acquire the library of hybrids, 9a‐r. The structural confirmations were availed by 1H‐NMR, 13C‐NMR, and IR techniques. The whole series was evaluated for biological potential against acetylcholinesterase (AChE) and α‐glucosidase enzymes. The biological evaluation ranges low to high in potential for different compounds based on the structural variations of synthesized compounds. Almost all the compounds remained active against both the enzymes except a few ones. The bovine serum albumin (BSA) binding study demonstrated the flow of drug in the body, and the docking study explained the interactions responsible for active behavior of synthesized compounds.

Exploring the Synergistic Anticancer Potential of Benzofuran–Oxadiazoles and Triazoles: Improved Ultrasound- and Microwave-Assisted Synthesis, Molecular Docking, Hemolytic, Thrombolytic and Anticancer Evaluation of Furan-Based Molecules

“…Method B: Microwave-assisted method [ 31 , 32 , 33 ] . Benzofuran–oxadiazole hybrid 3 (0.03 g, 0.137 mmol) and 5-(benzofuran-2-yl)-4-phenyl-4 H -1,2,4-triazole-3-thiol 6 (0.03 g, 0.103 mmol) were dissolved in DMF (25 mL).…”

Comparative conventional and microwave assisted synthesis of heterocyclic oxadiazole analogues having enzymatic inhibition potential

“…Pierre's protocol with slight changes was used in order to perform α‐glucosidase assay. [ 16 ] Alpha‐Glucosidase was from yeast. Reaction mixture containing 10 μL of purified enzyme (α‐glucosidase) was taken in buffer phosphate (6.8 pH) and 10 μL of test substance was incubated at 37°C for time duration of 10 minutes.…”

“…Pre‐reported method was used to perform AChE assay with necessary modifications. [ 1,16 ] AChE was from electric eel. Total volume of 100 μL of reaction mixture was prepared by adding 10 μL of enzyme (0.005 per unit well), 60 μL of Na 2 PO 4 buffer solution (50 mM, 7.7 pH) and 10 μL of test compound (0.5 mM per well).…”

“…BChE activity was performed by using reported method. [ 20 ] BChE was from equine. Briefly, 100 μL of reaction mixture having 60 μL of buffer solution (Na 2 PO 4 ) with 7.7 pH and 50 mM concentration, 10 μL test compound (0.5 mM per well) and 10 μL of butyryl cholinesterase enzyme.…”

“…Anti-α-glucosidase drugs candidates reduce conversion of carbohydrates into D-glucose which results in delayed glucose absorption and ultimately hyperglycemia is reduced, so such drugs can be used as anti-diabetic drug. [16] Cholinesterase enzymes (AChE and BChE) are serine hydrolases and are responsible for the termination of neurotransmitter acetylcholine through hydrolysis at cholinergic synapses leading to cholinergic brain synapses and neuromuscular junctions. [17] The current research involved the synthesis of N-substituted propanamide derivatives of 1,3,4-oxadiazole through comparative conventional and microwave assisted protocols.…”