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In the present study, a series of new carbazole linked 1 H -1,2,3-triazoles ( 2 – 27 ) were synthesized via click reaction of N -propargyl-9H-carbazole ( 1 ) and azides of appropriate acetophenones and heterocycles. Synthesized carbazole triazoles including 7 , 9 , 10 , 19 , 20 , and 23 – 26 (IC 50 = 0.8 ± 0.01–100.8 ± 3.6 μM), exhibited several folds more potent α -glucosidase inhibitory in vitro activity as compared to standard drug, acarbose. Compounds 2 – 5 , 7 – 13 , and 17 – 27 did not show any cytotoxicity against 3T3 cell lines, except triazoles 6 , and 14 – 16 . Among the series, carbazole triazoles 23 (IC 50 = 1.0 ± 0.057 μM) and 25 (IC 50 = 0.8 ± 0.01 μM) were found to be most active, and could serve as an attractive building block in the search of new non-sugar derivatives as anti-diabetic agents. [ABSTRACT FROM AUTHOR]

• Celebrex derivatives were synthesized as potent α -glucosidase inhibitors. • Celebrex analogue with 3′′′-nitro-4′′′-methyl substituents was the most active analogue (IC 50 = 92.32 ± 1.53 µM). • Mode of inhibition of synthesized compounds was studied using enzyme kinetics. • Molecular docking studies of active compounds showed significant binding interactions with critical amino acid residues (His280, Tyr158, and Arg315) of enzyme. Celebrex (1), commonly used as an anti-inflammatory drug, was functionalized (compounds 2 – 9) to identify new α -glucosidase inhibitors. Initially, all the synthesized derivatives were evaluated for anti-inflammatory activity but none was found to be active. Subsequently a random biological screening was carried out. Interestingly many of them were found to be potent α -glucosidase inhibitors in vitro. All the structures of synthesized derivatives were deduced through 1H NMR, FAB-MS, HR-MS, FT-IR analysis. The single-crystal X-ray structures of compounds 1 , and 5 further confirmed the assigned structures. Compounds exhibited a potent α -glucosidase inhibitory activity (IC 50 = 92.32 ± 1.530–445.20 ± 1.04 µM) against tested standard acarbose (IC 50 = 875.75 ± 2.08 µM), except compounds 2 and 4 , which appeared as inactive. Among them, compound 9 (IC 50 = 92.32 ± 1.530 µM) was the most potent inhibitor of α -glucosidase enzyme. Molecular docking studies revealed that compounds 6 , and 9 interacted with the key amino acid residues of α -glucosidase via H-bonding, and π-π stacking interactions. α -Glucosidase is a key target for the anti-diabetic drug development, and its inhibitors are known to exert anti hyperglycemic effect and help in lowering of post-prandial blood glucose levels. [ABSTRACT FROM AUTHOR]

[Display omitted] • Seven alkaloids were isolated from the roots of Berberis parkeriana Schneid. • Nine new derivatives of jatrorrhizine were chemically synthesized. • Compounds showed selective inhibition against butyrylcholinesterase enzyme (IC 50 = 5.5 ± 0.3 – 124.5 ± 0.4 µM). • Enzyme inhibition interactions were studied by molecular docking and kinetics. Seven known isoquinoline alkaloids 1 – 7 were isolated from the root extracts of Berberis parkeriana Schneid. Nine new derivatives 8 – 16 of one of the isolated compounds, jatrorrhizine (7), were synthesized. All the isolated as well as derivatized compounds were evaluated for their in - vitro acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activity. Functionalized compounds selectively exhibited a potent-to-moderate activity with IC 50 = 5.5 ± 0.3–124.5 ± 0.4 μM against butyrylcholinesterase enzyme. Among them, compound 15 was a potent BChE inhibitor (IC 50 = 5.5 ± 0.3 μM), as compared to the standard drug galantamine hydrobromide (IC 50 = 40.83 ± 0.37 μM). Active compounds were further subjected to kinetic, and molecular docking studies to predict their modes of inhibition, and interactions with the receptor (BChE), respectively. Enzyme kinetics studies showed that compounds 9 (IC 50 = 25.3 ± 0.5 μM), and 14 (IC 50 = 23.9 ± 0.5 μM) were non-competitive inhibitors, while compound 15 exhibited a competitive inhibition. In addition, these compounds were found to be non-cytotoxic against human fibroblast (BJ) cell line, except 9 (IC 50 = 17.1 ± 1.0 μM), and 10 (IC 50 = 18.4 ± 0.3 μM). Inhibition of cholinesterases is an important approach for development of drugs against Alzheimer's disease, and thus discoveries presented here deserve further investigation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of of new clioquinol derivatives 2a-11a were synthesized. • The synthetic compounds were evaluated for α-glucosidase inhibitory activity with IC 50 between 43.86 and 325.81 µM. • Kinetic studies of compounds 2a-11a indicated mode of inhibitions. • Docking studies on compounds 4a , 10a , and 11a revealed the predicted binding pose and their interactions with a-glucosidase. Diabetes mellitus is a chronic metabolic disorder with increasing prevalence and long-term complications. The aim of this study was to identify α- glucosidase inhibitory compounds with potential anti-hyperglycemic activity. For this purpose, a series of new clioquinol derivatives 2a-11a was synthesized, and characterized by various spectroscopic techniques. The enzyme inhibitory activities of the resulting derivatives were assessed using an in-vitro mechanism-based assay. All the tested compounds 2a-11a of the series showed a significant α- glucosidase inhibition with IC 50 values 43.86–325.81 µM, as compared to the standard drug acarbose 1C 50 : 875.75 ± 2.08 µM. Among them, compounds 4a , 5a , 10a , and 11a showed IC 50 values of 105.51 ± 2.41, 119.24 ± 2.37, 99.15 ± 2.06, and 43.86 ± 2.71 µM, respectively. Kinetic study of the active analogues showed competitive, non-competitive, and mixed-type inhibitions. Furthermore, the molecular docking study was performed to elucidate the binding interactions of most active analogues with the various sites of α-glucosidase enzyme. The results indicate that these compounds have the potential to be further studied as new anti-diabetic agents. [ABSTRACT FROM AUTHOR]