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In the presented work, we report the synthesis of a new series of sulfonamide-phosphonate hybrids 4a-m. These newly synthesized compounds were assessed for their inhibitory effects toward two human carbonic anhydrase isoforms I and II (hCA I and II). These examined isoforms were as well inhibited by the most of prepared sulfonamide-phosphonates in comparison to standard inhibitor acetazolamide. Obtained data exhibited that compounds 4b-m with Ki values in the range of 8.11–48.08 nM were more potent than standard drug acetazolamide with Ki value of 64.52 Nm against hCA I. Moreover, all the synthesized compounds (Ki values = 7.08–64.24 nM), with the exception of compound 4b, were more potent than acetazolamide (Ki value = 75.36) against hCA II. In particular, sulfonamide-phosphonates 4l and 4j, respectively, with substituents 5‑chloro-2-nitro and 2,3-dichloro emerged as the most potent hCA inhibitors. Thereafter, the molecular docking of compounds 4l and 4j at hCA I and II active sites was performed and the obtained results revealed that these compounds interacted whit the important amino acids of the active site. Finally, the predicted parameters of Lipinski's rule of five, ADME, and toxicity analysis showed that compounds 4l and 4j had good drug-likeness and acceptable physicochemical properties. Therefore, the hybridization of the sulfonamide and phosphonate moieties could be promising strategy for achieve to potent lead compounds for inhibition of hCA.

Background A new series of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide hybrids 11a-o was designed based on molecular hybridization of the active pharmacophores of the potent α-glucosidase inhibitors. These compounds were synthesized and evaluated against α-glucosidase. Methods The fifteen various derivatives of indole-carbohydrazide-phenoxy-1,2,3-triazole-N-phenylacetamide scaffold were synthesized, purified, and fully characterized. These derivatives were evaluated against yeast α-glucosidase in vitro and in silico. ADMET properties of the most potent compounds were also predicted. Results All new derivatives 11a-o (IC50 values = 6.31 ± 0.03–49.89 ± 0.09 µM) are excellent α-glucosidase inhibitors in comparison to acarbose (IC50 value = 750.0 ± 10.0 µM) that was used as a positive control. Representatively, (E)-2-(4-((4-((2-(1H-indole-2-carbonyl)hydrazono)methyl) phenoxy)methyl)-1H-1,2,3-triazol-1-yl)-N-(4-methoxyphenyl)acetamide 11d with IC50 = 6.31 µM against MCF-7 cells, was 118.8-times more potent than acarbose. This compound is an uncompetitive inhibitor against α-glucosidase and showed the lowest binding energy at the active site of this enzyme in comparison to other potent compounds. Furthermore, computational calculations predicted that compound 11d can be an orally active compound. Conclusion According to obtained data, compound 11d can be a valuable lead compound for further structural development and assessments to obtain effective and potent new α-glucosidase inhibitors.

Herein, a new series of 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors was designed and synthesized. All the synthesized compounds exhibited excellent inhibition potencies (IC50 values = 55.6–149.2 μM) against α-glucosidase when compared with the standard inhibitor acarbose (IC50 = 750.0 μM). Among the newly synthesized compounds, 4-methyl, 4-methoxy, and 2,3-dichloro derivatives exhibited the highest anti-α-glucosidase activities and were also non-cytotoxic against human normal dermal fibroblast cells. In silico druglikeness, ADME, and toxicity studies of these compounds were performed and obtained results were compared with acarbose. All the synthesized compounds were also inactive against α-amylase in comparison to acarbose. Kinetic study of the most potent compound, 4-methyl derivative, against α-glucosidase demonstrated that this compound is a competitive inhibitor. Furthermore, in silicoinduced fit docking and molecular dynamic studies were performed to further investigate the interaction, orientation, and conformation of these compounds over the active site of α-glycosidase.

α-Glucosidase is responsible for glucose release of oligosaccharides and disaccharides in the intestine and increase postprandial hyperglycemia. Inhibition of this enzyme is a beneficial therapeutic method for glycemic control in diabetes. This study deals with the design and synthesis of 4,5-diphenylimidazole-N-phenylacetamide derivatives 7a–l and the screen of these compounds for their potential for α-glucosidase inhibition. All the synthesized compounds exhibited superior α-glucosidase inhibition (IC50 = 90.0–598.5 µM) as compared to standard inhibitor acarbose (IC50 = 750.0 µM). In contrast, these compounds were inactive against α-amylase. Among the synthesized compounds, compound 7h was the most potent inhibitor of this library and was a competitive inhibitor into α-glucosidase with Ki value = 86.3 μM. Docking study of the most potent compounds was performed to evaluate the binding interactions of these compounds with the active site of enzyme and to determine of binding energies of ligand–enzyme complexes. The results of this in silico study are in complete agreement with the results obtained from in vitro α-glucosidase inhibition assay. Docking study of the most potent compound demonstrated that it interacted with important residues in the active site of α-glucosidase. In vitro cytotoxic activity of the most potent compounds and in silico druglikeness/ADME/toxicity study of these compounds were evaluated.

A new series of metronidazole-1,2,3-triazole derivatives 6a–o was synthesized and evaluated as Helicobacter pylori urease inhibitors. All the synthesized compounds were more potent than standard inhibitor thiourea against urease. Among the synthesized compounds, compound 6f (IC50 = 1.975 ± 0.25 µM) with inhibitory activity around 11-fols more than thiourea (IC50 = 22.00 ± 0.14 µM) was the most potent compound. Kinetic study of this compound revealed that compound 6f inhibited urease in an uncompetitive mode. Based on molecular modeling study, compound 6f pointed toward the bi-nickel center and stabilized by H-bond and T-shape π–π hydrophobic interactions with the critical residues His492 and Asp633. Moreover, it anchored to the helix-turn-helix motif in the active site cavity through interaction with His593 and Arg609. Consequently, it proposed that compound 6f through stabilization of active site flap inhibited urease activity.

A new series of spiro[indene-1,2'-quinazolin]-4'(3'H)-one derivatives 4a-m were synthesized via a one-pot method and evaluated for anticonvulsant activities using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced seizures. Obtained results demonstrated that these compounds have not anticonvulsant activity in PTZ test while are active in the MES test. Among the synthesized compounds, the best anticonvulsant activity was obtained with compound 4h. This compound also was not neurotoxic. Given that the title new compounds have the pharmacophore requirement for benzodiazepine (BZD) receptor agonist, the most potent compound was assayed in vivo and in silico as BZD receptor agonist. After treatment with flumazenil as a standard BZD receptor antagonist, anticonvulsant activity of compound 4h decreased. Therefore, the involvement of BZD receptors in anticonvulsant activity of this compound confirmed. Furthermore, docking study of compound 4h in the BZD-binding site of GABA

Background: α-Glucosidase is a hydrolyzing enzyme that plays a crucial role in the degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained from the reaction between 4-(bromomethyl)-7- methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence of potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, a docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as a standard inhibitor (IC50 = 750.0 ± 9.0 μM). Among them, the secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound competes with a substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Moreover, a molecular docking study predicted that this compound interacted with the α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for designing potent α-glucosidase inhibitors for the treatment of type 2 diabetes.

In this study, a new series of quinazolinone-1,2,3-triazole-acetamide hybrids 8a–m, using by molecular hybridization of the potent α-glucosidase inhibitor pharmacophores, was designed and evaluated against carbohydrate-hydrolyzing enzymes α-glucosidase and α-amylase. All the synthesized compounds with IC50 values in the range of 45.3 ± 1.4 µM to 195.5 ± 4.7 µM were significantly more potent than standard inhibitor against α-glucosidase, while these compounds were not active against α-amylase in comparison to standard inhibitor. Representatively, compound 8a with IC50 = 45.3 ± 1.4 µM was around 17 times more potent than standard inhibitor acarbose (IC50 = 750.0 ± 12.5 µM). The inhibition kinetic analysis of the compound 8a indicated that this compound was a competitive α-glucosidase inhibitor. Molecular modeling analysis confirmed that the most potent inhibitors 8a and 8b well accommodated in the modeled α-glucosidase active site and it was also revealed that these compounds formed stable inhibitor–receptor complexes with the α-glucosidase in comparison to acarbose. In silico pharmacokinetic and toxicity of the most potent compounds were evaluated and obtained results were compared with acarbose. Furthermore, the most potent compounds were also evaluated against human normal cells and no cytotoxicity was observed.

In this work, new indole-acrylamide-1,2,3-triazole derivatives 9a–j were synthesized via simple and efficient chemical reactions and screened for in vitro anti-α-glucosidase activities. All the synthesized derivatives exhibited excellent α-glucosidase inhibition in the range of IC50 = 65.0 ± 0.8 − 396.3 ± 0.7 µM as compared to the standard inhibitor acarbose (IC50 = 750.0 ± 1.5 µM). Furthermore, kinetic, docking, and toxicity evaluation of the title compounds were also performed.

In the design of novel drugs, the formation of hybrid molecules via the combination of several pharmacophores can give rise to compounds with interesting biochemical profiles. A series of novel quinazolin-sulfonamid derivatives (

In this study, a novel series of 2,4-dioxochroman-1,2,3-triazole hybrids 8a-l was synthesized by click reaction. These compounds were screened against α-glucosidase through in vitro and in silico evaluations. All the synthesized hybrids exhibited excellent α-glucosidase inhibition in comparison to standard drug acarbose. Representatively, 3-((((1-(3,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl)methyl)amino)methylene)chroman-2,4- dione 8h with IC50 = 20.1 ± 1.5 μM against α-glucosidase, was 37-times more potent than acarbose. Enzyme kinetic study revealed that compound 8h was a competitive inhibitor against α-glucosidase. In silico docking study on chloro derivatives 8h, 8g, and 8i were also performed in the active site of α -glucosidase. Evaluations on obtained interaction modes and binding energies of these compounds confirmed the results obtained through in vitro α-glucosidase inhibition.

A novel series of (thio)barbituric-phenoxy-N-phenylacetamide derivatives 7a-l was synthesized and evaluated against Helicobacter pylori urease. The latter assay revealed that all the synthesized compounds 7a-l (IC50 = 0.69 ± 0.33–2.47 ± 0.23 μM) were significantly more potent than two used standard inhibitors, thiourea (IC50 = 23 ± 0.73 μM) and hydroxyurea (IC50 = 100 ± 1.7 μM). Docking study of the synthesized compounds demonstrated that these compounds as well fitted in the urease active site. Moreover, molecular dynamic study of the most potent compound 7d showed that this compound created important interactions with the active site flap residues, Cys592 and His593. Furthermore, in silico pharmacokinetic study predicted that all the synthesized compounds are drug-like.

α-Glucosidase plays a major role in degradation of carbohydrates to glucose. Therefore, inhibition of this enzyme can be useful in the treatment of carbohydrate-related diseases such as diabetes, cancer, and viral infections. In this study, a new series of acridine-9-carboxamide linked to 1,2,3-triazole-N-phenylacetamide derivatives 5a–m were designed, synthesized, and evaluated as potent α-glucosidase inhibitors. All the synthesized compounds showed excellent to good inhibitory activity against α-glucosidase with IC50 values of 80.3 ± 0.9–564.3 ± 7.2 µM in comparison with standard drug acarbose (IC50 value = 750.0 ± 10.5 μM). Among the synthesized compounds, the most active compound was 3-bromo derivative 5h with inhibitory activity around 9.3 times more than acarbose. this compound was selected for farther biological evaluations. Kinetic study of compound 5h revealed that it is a competitive inhibitor against α-glucosidase. Docking study of compound 5h and its regioisomer 5i with 4-bromo substituent were also carried out in the active site of α-glucosidase to gain an insight into the interaction modes of the synthesized compounds and rationalized structure–activity relationship between these two compounds. Compound 5h was also evaluated against α-amylase and no activity was observed in comparison with acarbose. Furthermore, in vitro cytotoxic assay of compound 5h against human normal and cancer cell lines HDF and MCF-7, respectively, revealed that this compound is a noncytotoxic agent. In silico pharmacokinetic and toxicity assays of compound 5h was performed and obtained results were compared with acarbose.

We have designed and synthesized phthalimide-Schiff base-coumarin hybrids 8a–b, 9a–d, 10a–b, and 11a–d and evaluated them for α-glucosidase inhibitory potential against yeast form of this enzyme. For the synthesis of title compounds 4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-hydroxybenzaldehyde, 2-hydroxybenzaldehyde derivatives, coumarin-3-carbohydrazide, and coumarin-7-yloxy-acetohydrazide were used. In vitro α-glucosidase inhibition revealed that all the synthesized compounds exhibited outstanding α-glucosidase inhibition with IC50 values ranging between 85.2 ± 1.7 and 577.7 ± 7.5 µM when compared with the standard inhibitor acarbose having IC50 value 750.0 ± 12.0 µM. The most potent compounds were 4-hydroxybenzaldehyde derivative 8a with coumarin-3-carbohydrazide moiety, 2-hydroxy-5-nitrobenzaldehyde derivative 11d with coumarin-7-yloxy-acetohydrazide moiety, and 2-hydroxy-5-nitrobenzaldehyde derivative 9d with coumarin-3-carbohydrazide moiety. Molecular docking studies were carried out to understand the interaction modes and binding energies of the most active compounds and standard drug acarbose. This studies predicted that compounds 8a, 11d, and 9d (respectively with binding energies = − 10.77, − 8.65, and − 8.66 kcal/mol) bind to active site α-glucosidase more easily than acarbose (binding energy = − 4.04 kcal/mol).

A novel series of N-phenylacetamide-oxindole-thiosemicarbazide hybrids were synthesized and evaluated for their tyrosinase inhibitory activity. According to tyrosinase inhibition results, all the synthesized compounds showed high tyrosinase inhibitory activity with IC

In this study, 18 novel quinoline-based-benzo[d]imidazole derivatives were synthesized and screened for their α-glucosidase inhibitory potential. All compounds in the series except 9q showed a significant α-glucosidase inhibition with IC50 values in the range of 3.2 ± 0.3–185.0 ± 0.3 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 5.0 µM). A kinetic study indicated that compound 9d as the most potent derivative against α-glucosidase was a competitive type inhibitor. Furthermore, the molecular docking study revealed the effective binding interactions of 9d with the active site of the α-glucosidase enzyme. The results indicate that the designed compounds have the potential to be further studied as new anti-diabetic agents.

A series of novel 4-phenylpiperazine-carbodithioate-N-phenylacetamide hybrids (6a-n) was designed, synthesized, and evaluated for their in vitro inhibitory activity against the metabolic enzymes, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The obtained results showed that most of the synthesized compounds exhibited high to good anti-AChE and anti-BChE activity in the range of nanomolar concentrations in comparison to tacrine as a positive control. Molecular modeling of the most potent compounds 6e and 6i demonstrated that these compounds interacted with important residues of the AChE and BChE active sites. Moreover, all the newly synthesized compounds 6a-n had significant K

A new series of phthalimide-benzamide-1,2,3-triazole hybrids 8a–k as α-glucosidase inhibitors was designed and synthesized. The biological evaluation of compounds 8a–k against yeast α-glucosidase demonstrated that all they have excellent inhibitory activity in comparison with standard inhibitor acarbose. Among them, the most potent compound was compound 8d with inhibitory activity 18.5-fold more than acarbose. Kinetic study revealed that α-glucosidase inhibition of compound 8d was the competitive type. Furthermore, docking study suggested that compound 8d is more stable than acarbose in the active site of α-glucosidase.

A new series of 4-oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide hybrids 8a–p was designed, synthesized, and screened as the potential cholinesterase inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Obtained anti-cholinesterase activities demonstrated that all the title compounds exhibited excellent inhibition against BuChE and moderate inhibitory activity toward AChE in comparison to standard cholinesterase inhibitor donepezil. For example, compound 8e exhibited about 49-fold higher inhibitory activity than donepezil (IC50 = 3.2 ± 0.3 μM) against BuChE. This compound inhibited BuChE via a mixed-type inhibition mode. This finding demonstrated that compound 8e in addition to catalytic anionic site (CAS) can also interact with the peripheral anionic site (PAS) of BuChE. Molecular modeling and molecular dynamic studies were also performed on synthesized compounds.

A new series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o has been synthesized, characterized by 1H NMR, 13C NMR, and screened for their in vitro α-glucosidase inhibitory activity. All of the synthesized compounds displayed excellent α-glucosidase inhibitory activity with IC50 values in the range of 75.0 ± 0.5 to 253.0 ± 0.5 μM, as compared to the standard drug acarbose (IC50 = 750.0 ± 1.5 μM). Among the synthesized compounds, compound 10h (IC50 = 75.0 ± 0.5) with 4-methoxy group at phenyl part of thiosemicarbazide moiety and 2,6-dichloro substituents at benzyl moiety was found to be the most potent compound. Kinetic analysis revealed that compound 10h is a competitive inhibitor for α-glucosidase. Docking study of compound 10h in the active site of α-glucosidase showed that this compound interacted with residues His239, His279, Glu304, Gly306, and Arg312.

The Ugi four-component (Ugi-4CR) post-transformation reactions have emerged as a prominent tool to construct complex organic molecules utilizing readily available starting materials. Propiolic acid derivatives are promising choice of substrates due to their versatile reactivity. Over the last decade, Ugi post-transformations starting from propiolic acid derivatives have experienced a rapid growth to afford atom-efficient processes and enantioselective transformations. This review has focused on the recent advances in the Ugi post-transformations starting from propiolic acids and their application for the preparation of highly functionalized organic compounds.

Novel 4-oxobenzo[d]1,2,3-triazin derivatives bearing pyridinium moiety 6a–q were synthesized and screened against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Most of the synthesized compounds showed good inhibitory activity against AChE. Among the synthesized compounds, the compound 6j exhibited the highest AChE inhibitory activity. It should be noted that these compounds displayed low anti-BuChE activity with the exception of the compound 6i, as it exhibited BuChE inhibitory activity more than donepezil. The kinetic study of the compound 6j revealed that this compound inhibited AChE in a mixed-type inhibition mode. This finding was also confirmed by the docking study. The latter study demonstrated that the compound 6j interacted with both the catalytic site and peripheral anionic site of the AChE active site. The compound 6j was also observed to have significant neuroprotective activity against H2O2-induced PC12 oxidative stress, but low activity against β-secretase.

Background: This work reports design, synthesis, and in vitro cytotoxicity of novel coumarin-1,2,3-triazole-1,2,4-oxadiazole hybrids against three breast cancer cell lines MCF-7, MDA-MB-231, and T-47D. Methods: Synthetic procedure for the preparation of desired compounds was started from the reaction of coumarins or with propargyl bromide to give O-propargylated coumarins or 5. Then, click reaction between the later compounds and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles afforded the desired products in good yields. Results: Among the synthesized compounds, 4-((1-((3-(4-chlorophenyl)-1,2,4-oxadiazol-5- yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one (9a) showed the best cytotoxicity against breast cancer cell lines. Conclusion: Compound 9a depicted the most activity toward MDA-MB-231 and T-47D cells while compounds 8a and 8c were the most potent compounds against MCF-7.

In the development of novel anti-α-glucosidase agents, we synthesized novel thieno[2,3-b]quinoline-hydrazones 9a-n by facile and efficient conventional chemical reactions. These compounds were characterized by IR

A series of 5-nitrofuran-2-yl-thiadiazole linked to different cyclohexyl-2-(phenylamino)acetamides were rationally designed and synthesized. All synthetic compounds were evaluated for their urease inhibitory activity and exhibited good inhibitory potential against urease with IC

A new series of quinoxalin-1,3,4-oxadiazole (10a-l) derivatives was synthesized and evaluated against some metabolic enzymes including human carbonic anhydrase (hCA) isoenzymes I and II (carbonic anhydrases I and II), cholinesterase (acetylcholinesterase and butyrylcholinesterase), and α-glucosidase. Obtained data revealed that all the synthesized compounds were more potent as compared with the used standard inhibitors against studied target enzymes. Among the synthesized compounds, 4-fluoro derivative (10f) against hCA I, 4-chloro derivative (10i) against hCA II, 3-fluoro derivative (10e) against acetylcholinesterase and butyrylcholinesterase, and 3-bromo derivative (10k) against α-glucosidase were the most potent compounds with inhibitory activity around 1.8- to 7.37-fold better than standard inhibitors. Furthermore, docking studies of these compounds were performed at the active site of their target enzymes.

Background and purpose: Although pain is one of the most common symptoms of diseases, it is often mismanaged due to limited access to painkillers and ineffectiveness, unacceptable side effects, or the possibility of abuse. However, an alternative approach to existing analgesics is to indirectly increase endogenous pain relief pathways by neprilysin (an enkephalinase) inhibitors. This enzyme breaks down and inactivates enkephalin, dynorphin, endorphins, and their derivatives. Experimental approach: In this project, a new series of racecadotril-tetrazole-amino acid derivatives 15a-l was synthesized and characterized on the basis of IR, 1H and 13C NMR, mass spectrometry, and elemental analysis. The antinociceptive activity of synthesized compounds was assessed by a hot plate, tail-flick, and formalin assays in mice. Docking was used to identify the possible interactions between neprilysin and synthesized compounds. 15a-l was synthesized and characterized on the basis of IR, 1H and 13C NMR, mass spectrometry, and elemental analysis. The antinociceptive activity of synthesized compounds was assessed by a hot plate, tail-flick, and formalin assays in mice. Docking was used to identify the possible interactions between neprilysin and synthesized compounds. Findings/Results: Most of the synthesized compounds showed moderate to good analgesic effects in hot plat and tail-flick test in comparison to morphine and racecadotril. Compounds 15l and 15j were the most potent compounds. The synergistic analgesic effect of compounds 15l and 15j with morphine and the antagonistic effect of naloxone on the activity of these compounds confirm that the analgesic effect of compounds 15l and 15j could be mediated through the opioidergic system. The negative and high binding energy of docking simulation of the most potent compounds in the catalytic site of neprilysin was also in good agreement with the inhibitory activity of test compounds. Conclusion and implications: Racecadotril-tetrazole-amino acid derivatives, as potential antinociceptive agents, demonstrated moderate to good antinociceptive activities comparable with morphine and higher than racecadotril.

A new series of quinazolinone-2-thio-metronidazole derivatives 9a-o was designed, synthesized and assayed for their activities against metabolic enzymes human carbonic anhydrase I and II (hCAs I and II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against CA enzymes, 4-fluorophenyl derivative 9i, was 4 and 7-times more potent than standard inhibitor acetazolamide against hCA I and II, respectively; 4-fluorobenzyl derivative 9m as the most potent compound against cholinesterase enzymes, was around 11 and 21-times more potent than standard inhibitor tacrine against AChE and BChE, respectively; the most active α-glucosidase inhibitor 9h with 4-methoxyphenyl moiety was 5-times more active that acarbose as standard inhibitor. Furthermore, in order to study interaction modes of the most potent compounds in the active site of their related enzymes, molecular modeling was performed. Druglikeness, ADME, and toxicity profile of the compounds 9i, 9m, and 9h were also predicted.