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To explore new scaffolds for the treat of Alzheimer's disease appears to be an inspiring goal. In this context, a series of varyingly substituted flavonols and 4-thioflavonols have been designed and synthesized efficiently. All the newly synthesized compounds were characterized unambiguously by common spectroscopic techniques (IR, 1 H-, 13 C NMR) and mass spectrometry (EI-MS). All the derivatives (1-24) were evaluated in vitro for their inhibitory potential against cholinesterase enzymes. The results exhibited that these derivatives were potent selective inhibitors of acetylcholinesterase (AChE), except the compound 11 which was selective inhibitor of butyrylcholinesterase (BChE), with varying degree of IC 50 values. Remarkably, the compounds 20 and 23 have been found the most potent almost dual inhibitors of AChE and BChE amongst the series with IC 50 values even less than the standard drug. The experimental results in silico were further validated by molecular docking studies in order to find their binding modes with the active pockets of AChE and BChE enzymes., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The prime objective of this research work is to prepare readily soluble synthetic analogues of naturally occurring 3- O -flavonol glycosides and then investigate the influence of various substituents on biological properties of synthetic compounds. In this context, a series of varyingly substituted 3- O -flavonol glycosides have been designed, synthesized and characterized efficiently. The structures of synthetic molecules were unambiguously corroborated by IR, 1 H, 13 C NMR and ESI-MS spectroscopic techniques. The structure of compound 22 was also analyzed by X-ray diffraction analysis. All the synthetic compounds ( 21 – 30 ) were evaluated for in vitro inhibitory potential against cholinesterase enzymes. The results displayed that most of the derivatives were potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with varying degree of IC 50 values. The experimental results were further encouraged by molecular docking studies in order to explore their binding behavior with the active pocket of AChE and BChE enzymes. The experimental and theoretical results are in parallel with one another. [ABSTRACT FROM AUTHOR]

In this study, a library of new intriguing flavonol derivatives (1 – 17) was designed and synthesized through a facile route involving Algar-Flynn-Oyamada reaction in a one-pot synthesis. The molecular structures of all newly synthesized compounds were unequivocally corroborated by different spectroscopic techniques such as FTIR, UV–Vis, 1H NMR and 13C NMR and mass spectrometry (EI-MS). All the synthesized analogs (1-17) were evaluated in vitro for their inhibitory potential against ɑ-amylase and ɑ-glucosidase enzymes. Interestingly, all the synthetic compounds displayed good to moderate inhibition potential with IC 50 values ranging from 4.86 ± 1.39 to 265.61 ± 5.85 μ M for a -amylase, and 70.57 ± 1.13 to 322.98 ± 4.43 μ M for a -glucosidase in comparison to the standard acarbose (IC 50 = 5.03 ± 9.44 μ M for a -amylase and IC 50 = 75.26 ± 0.15 μ M for α -glucosidase). It is worth mentioning that amongst the series, the compounds 9 (IC 50 = 4.86 ± 1.39 μ M for a -amylase and IC 50 = 70.57 ± 1.13 μ M for α -glucosidase) and 14 (IC 50 = 5.02 ± 1.35 for a -amylase and IC 50 = 71.69 ± 5.85 μ M for α -glucosidase) were found the most potent dual inhibitors, even more active than standard. Furthermore, the target compounds (1-17) exhibited moderate to good antioxidant activities. Molecular simulations studies were conducted to correlate the in vitro results and to identify the possible mode of binding interaction of ligands with the active site of enzymes. Moreover, molecular description was performed with the drug-likeness and bioactivity scores. The results showed that some compounds are in a linear correlation with Lipinski's rule of five demonstrating good drug-likeness and bioactivity score for drug targets. Structure-activity relationships delivered useful insights towards this class of compounds, and thus paved the way to design novel analogs with improved potency. Image 1 • Seventeen brominated-flavonol derivatives were synthesized and characterized. • In vitro evaluation of prepared compounds against a- amylase and a- glucosidase enzymes. • Limited structure-activity relationship was established. • Molecular modelling studies of most active compounds for both enzymes. • The drug-likeness and bioactivity scores were calculated and interpreted. [ABSTRACT FROM AUTHOR]