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Two new binuclear Cu(II) complexes represented by the general formula {(dmso)Cu(μ-L)4Cu(dmso)} (1) and {(Phen)(L)Cu(μ-L)2Cu(L)(Phen)} (2) where dmso = dimethyl sulphoxide, L = 2-bromophenyl acetate and Phen = = 1,10-phenanthroline have been synthesized, isolated quantitatively and characterized by UV/Vis and FT-IR spectroscopic techniques, thermogravimetry/ /differential thermal analysis and X-ray single crystal XRD studies. Complex 1 is paddlewheel with 1,2-O,O-bridging while 2 has 1,1-O-bridging. The values of the intrinsic binding constants with DNA were found out to be 2.0×103 and 1.1×103 M-1, respectively for compound 1 and 2. The mode of interaction of complexes with DNA was also evaluated through computational study by molecular docking (in silico) study using molecular operating environment (MOE) software. The synthesized complexes are structurally as well as biologically important.

Copper(II) complexes with a general formula [Cu2(3,4-F2C6H3CH2COO)4(L)2], where L = 2-methylpyridine (1) and 3-methylpyridine (2), are reported here. The FTIR spectra of the complexes confirmed the bridging bidentate coordination mode of the carboxylate ligand. The low (475 and 449 cm−1) and strong (727 & 725 cm−1) intensity bands in the FTIR spectra, due to Cu-N stretches and pyridyl ring vibrations, confirmed coordination of the 2-/3-methyl pyridine co-ligands in complexes 1 and 2, respectively. A binuclear paddlewheel structural arrangement with a square pyramidal geometry was confirmed for copper atoms in the complexes via single-crystal X-ray analysis. The DPPH, •OH radical, and α-amylase enzyme inhibition assays showed higher activities for the complexes than for the free ligand acid. The binding constant (Kb = 1.32 × 105 for 1 and 5.33 × 105 for 2) calculated via UV-VIS absorption measurements and docking scores (−6.59 for 1 and −7.43 for 2) calculated via molecular docking showed higher SS-DNA binding potential for 2 compared to 1. Viscosity measurement also reflected higher DNA binding ability for 2 than 1. Both complexes 1 and 2 (docking scores of −7.43 and −6.95, respectively) were found to be more active inhibitors than the free ligand acid (docking score of −5.5159) against the target α-amylase protein. This in silico study has shown that the herein reported compounds follow the rules of drug-likeness and exhibit good potential for bioavailability. [ABSTRACT FROM AUTHOR]

Herein, we present an experimental and theoretical drug–drug interaction study between nitazoxanide (NTZ) and azithromycin (AZT) in an aqueous solution. Interaction was studied by using UV/Vis, fluorescence, attenuated total reflectance‐fourier transform infrared (ATR‐FTIR), and circular dichroism (CD) spectroscopy, while molecular docking studies were performed to establish the interaction computationally. A bright yellow color was observed when the two drugs interacted, giving a hyperchromic band at 420 nm. The rate of absorbance was linearly increased by increasing drug concentrations and in a time‐dependent manner. Stability of the interaction complex (i.e., NTZ: AZT) was measured at variable temperatures (25–80°C), pH (5.0–10.0) and ionic strength (0.05–2.0 M NaCl), and not only proved stable but also retained antimicrobial potential with reduced cellular toxicity. Mole ratio and Job's method of continuous variations were used to establish the binding stoichiometry and found to be 2:1. The calculated binding constant (kb = 8,400 M−1) and Gibb's free energy (ΔG° = −22.4 KJ/mol) also suggested an energetically favorable interaction. FTIR spectra of NTZ: AZT complex in comparison with two drugs alone revealed significant interaction which was nicely complemented by molecular docking studies. Interaction was also successfully demonstrated in presence of carrier protein HSA and by spiking the two drugs in real samples of human plasma and urine. [ABSTRACT FROM AUTHOR]

Introduction: Monkeypox is a zoonotic disease caused by brick-shaped enveloped monkeypox (Mpox) virus that belongs to the family of ancient viruses known as Poxviridae. Subsequently, the viruses have been reported in various countries. The virus is transmitted by respiratory droplets, skin lesions, and infected body fluids. The infected patients experience fluid-filled blisters, maculopapular rash, myalgia, and fever. Due to the lack of effective drugs or vaccines, there is a need to identify the most potent and effective drugs to reduce the spread of monkeypox. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Mpox virus. Methods: In our study, the Mpox protein thymidylate kinase (A48R) was targeted because it is a unique drug target. We screened a library of 9000 FDA-approved compounds of the DrugBank database by using various in silico approaches, such as molecular docking and molecular dynamic (MD) simulation. Results: Based on docking score and interaction analysis, compounds DB12380, DB13276, DB13276, DB11740, DB14675, DB11978, DB08526, DB06573, DB15796, DB08223, DB11736, DB16250, and DB16335 were predicted as the most potent. To examine the dynamic behavior and stability of the docked complexes, three compounds--DB16335, DB15796, and DB16250--along with the Apo state were simulated for 300ns. The results revealed that compound DB16335 revealed the best docking score (-9.57 kcal/mol) against the Mpox protein thymidylate kinase. Discussion: Additionally, during the 300 ns MD simulation period, thymidylate kinase DB16335 showed great stability. Further, in vitro and in vivo study is recommended for the final predicted compounds. [ABSTRACT FROM AUTHOR]

Globally, novel coronavirus (nCoV19) outbreak is a great concern to humanity owing to the unavailability of effective medication or vaccine to date. Therefore, the development of drugs having anti-COVID-19 potential is a need of time. In this milieu, in-silico studies have proven to be rapid, inexpensive and effective as compared to other experimental studies. Evidently, natural products have shown significant potential in drug development to curtail different ailments, which have opened a new horizon in the screening of anti-COVID-19 agents. In this study, in-silico analysis were performed on derivatives of amentoflavone (4′, 4′′′-Dimethylamentoflavone, 4′′′, 7-Di-O-Methylamentoflavone, 4′′′′′′-methylamentoflavone, 4′-Monomethylamentoflavone, 7,4′-Dimethylamentoflavone, 7′-O-Methylamentoflavone, 7-O-methylamentoflavone, Heveaflavone, kayaflavone, and Sciadopitysin) and FDA approved anti-viral drug (camostatmesylate). All the derivatives of amentoflavone and FDA-approved anti-viral drugs were docked against SARS-CoV2 main protease (MPRO). The ten derivatives of amentoflavone showed strong interactions with the MPRO protein. In all cases, derivatives of amentoflavone showed good interaction with the targeted protein and better binding/docking score (–9.0351, –8.8566, –8.8509, –8.7746, –8.6192, –8.2537, –8.0876, –7.9501, –7.6429, and –7.6248 respectively) than FDA approved anti-viral drug. Therefore, derivatives of amentoflavone may be potent leads in drug discovery to combat HCoVs, such as SARS-CoV2. Moreover, to support the outcomes of this study further in-vivo investigations are required. [ABSTRACT FROM AUTHOR]

Diabetes is one of the main health issues worldwide because of its lifetime duration. To overcome this health problem, the current study was conducted. This investigation aims to explore the α-glucosidase and β-secretase potential of extract/fractions and pure isolated compounds of Syzygium cumini bark. The chloroform extract of Syzygium cumini bark was subjected to chromatographic analysis to yield compound 1. The structure of isolated phytochemical (1) was conducted using advanced spectroscopic analysis. Among test extracts, the chloroform fraction exhibited a significant effect against α-glucosidase with a % activity of 86.20% and an IC50 of 77.09 µM, while the isolated compound exhibited a promising effect with a % activity of 91.54 and an IC50 value of 17.54 μM. The extract/fractions and isolated compound 1 also showed promising effects against the β-secretase enzyme, having % effects of 83.21 and 91.54% with IC50 values of 318.76 and 17.54 μM, respectively. The extract/fractions and compound 1 were found to possess promising inhibitory activity against α-glucosidase and β-secretase. This research project opens a new avenue for research into detailed chemical and biological studies on Syzygium cumini to isolate bioactive enzyme inhibitors. Furthermore, the isolated compound 1 friedelin was docked into the active site of β-secretase and α-glucosidase. The molecular docking was assessed using molecular docking via the MOE-Dock tool. The docking results showed good docking scores of −6.84 and −6.46 when docked against β-secretase and α-glucosidase, respectively, and strong interactions. [ABSTRACT FROM AUTHOR]

Twenty-one analogs were synthesized based on benzimidazole, incorporating a substituted benzaldehyde moiety (1–21). These were then screened for their acetylcholinesterase and butyrylcholinesterase inhibition profiles. All the derivatives except 13, 14, and 20 showed various inhibitory potentials, ranging from IC50 values of 0.050 ± 0.001 µM to 25.30 ± 0.40 µM against acetylcholinesterase, and 0.080 ± 0.001 µM to 25.80 ± 0.40 µM against butyrylcholinesterase, when compared with the standard drug donepezil (0.016 ± 0.12 µM and 0.30 ± 0.010 µM, against acetylcholinesterase and butyrylcholinesterase, respectively). Compound 3 in both cases was found to be the most potent compound due to the presence of chloro groups at the 3 and 4 positions of the phenyl ring. A structure-activity relationship study was performed for all the analogs except 13, 14, and 20, further, molecular dynamics simulations were performed for the top two compounds as well as the reference compound in a complex with acetylcholinesterase and butyrylcholinesterase. The molecular dynamics simulation analysis revealed that compound 3 formed the most stable complex with both acetylcholinesterase and butyrylcholinesterase, followed by compound 10. As compared to the standard inhibitor donepezil both compounds revealed greater stabilities and higher binding affinities for both acetylcholinesterase and butyrylcholinesterase. [ABSTRACT FROM AUTHOR]

Infection of hepatitis C (HCV) is a major threat to human health throughout the world. The current therapy program suffers from restricted efficiency and low tolerance, and there is serious demand frr novel medication. NS3/4A protease is observed to be very effective target for the treatment of HCV. A data set of the already reported HCV NS3/4A protease inhibitors was first docked into the NS3/4A protease (PDB ID: 4A92A) active sites of both protease and helicase sites for calculating the docking score, binding affinity, binding mode, and solvation energy. Then the data set of these reported inhibitors was used in a computer-based program "RECAP Analyses" implemented in MOE to fragment every molecule in the subset according to simple retrosynthetic analysis rules. The RECAP analysis fragments were then used in another computer-based program "RECAP Synthesis" to randomly recombine and generate synthetically reasonable novel chemical structures. The novel chemical structures thus produced were then docked against HCV NS3/4A. After a thorough validation of all undertaken steps, based on Lipinski's rule of five, docking score, binding affinity, solvation energy, and Van der Waal's interactions with HCV NS3/4A, 12 novel chemical structures were identified as inhibitors of HCV NS3/4A. The novel structures thus designed are hoped to play a key role in the development of new effective inhibitors of HCV. [ABSTRACT FROM AUTHOR]

About 19 spirooxindole analogs 8 a–s engrafted with pyrazole scaffolds were designed and constructed via [3+2] cycloaddition reaction (32CA) approach. The synthesized spirooxindole analogs was screened for anti‐cholinesterase against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and antioxidant potentials against DPPH. The compounds 8 h and 8 i showed the strongest acetylcholine esterase (AChE) and butyrylcholinesterase (BChE) inhibition with IC50 values of 30 μg/mL respectively. The highest anti‐oxidant potential was demonstrated by compounds 8 p with IC50 values of 240 μg/mL, respectively. Molecular docking was used to study their interaction with the active site of enzymes. [ABSTRACT FROM AUTHOR]

Heterophragma adenophyllum is a traditional medicinal plant that has been used as anti-inflammatory and to relief muscular tension. In the current research, four isolated constitutes namely lapacho (1), peshawaraquinone (2), indanone derivatives (3), α-lapachone (4) of H. adenophyllum were tested for anti-inflammatory effect using the carrageenan- and histamine-induced paw edema paradigm. The tested compounds (1–4) were evaluated for anti-inflammatory effect during the early and late phase of edema induction. In the early phase, all tested compounds (0.5 2.5 mg/kg each i.p.) demonstrated less than 50% effect, while in the later phase, compounds (2 and 3) demonstrated 85.66 and 89.87% attenuation. In addition, compounds (1–4) were subjected to histamine-induced inflammation, where compounds 2 and 3 exhibited excellent effects 86.87 and 89.98%, respectively at 5 mg/kg after the 2nd hour of administration, whereas compounds 1 and 4 did not exhibit any significant effect as compared with the negative control. Molecular docking results revealed a very high potency of compound based on the protein-ligand interaction (PLI) profile, which was further evaluated through a molecular dynamic simulation study. Therefore, the anti-inflammatory effect of H. adenophyllum attributed to the presence of these bioactive compounds (1–4) strongly supports the traditional uses of H. adenophyllum for treatment of inflammation. However, compounds 2 and 3 which exerted anti-inflammatory effect must be subjected for further mechanistic studies. [ABSTRACT FROM AUTHOR]

Background: Analgesic, anti-inflammatory, and sedative drugs are available with potential side effects such as peptic ulcer and addiction among other things. In this regard, research is underway to find safe, effective, and economical drugs free of these side effects. In this study, an isolated natural product from Diospyros lotus, was tested for the aforementioned bioactivities. Objectives: To evaluate analgesic, anti-inflammatory, and sedative potential of D. lotus extracts in animal paradigms using BALB/c mice as experimental model. Methods: Analgesic, anti-inflammatory and sedative activities of dinaphthodiospyrol G (1) isolated from the chloroform fraction of D. lotus were evaluated using different experimental procedures. Anti-inflammatory effect was evaluated using the carrageenan and histamine-induced paw edema, whereas the antinociceptive effect was quantified by means of the hot plate analgesiometer. On the other hand, the sedative effect was determined using animal assay for screening the locomotors effects of compound 1. Compound 1 was also subjected to molecular modeling studies against cyclooxygenase enzymes. Results: Results from this investigation showed that the extract is devoid of anti-inflammatory and antinociceptive potentials but has a significant sedative effect, whereas the tested compound exhibited 55.23 and 78.34% attenuation in paw edema by carrageenan and histamine assays, respectively. A significant (p < 0.001) and dose-dependent antinociceptive and sedative effects were demonstrated by the isolated compound. Molecular docking and dynamics simulation studies of the isolated compound against cyclooxygenase enzyme indicated that compound 1 forms specific interactions with key residues in the active site of the target receptor, which validates the potential use of the isolated compound as cyclooxygenase inhibitor. Conclusions: Compound 1 exhibited remarkable analgesic, anti-inflammatory, and sedative activities. These findings strongly justify the traditional use of D. lotus in the treatment of inflammation, pain, and insomnia. [ABSTRACT FROM AUTHOR]

In continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1–14) were synthesized, characterized by HREI-MS, 1H and 13CNMR and evaluated for urease inhibition. Compounds 1–14 exhibited a varying degree of urease inhibitory activity with IC50 values between 1.2 ± 0.01 to 23.50 ± 0.70 µM when compared with standard drug thiourea having IC50 value 21.40 ± 0.21 µM. Compound 1, 3, 5 and 8 showed significant inhibitory effects with IC50 values 1.2 ± 0.01, 2.20 ± 0.01, 1.40 ± 0.01 and 2.90 ± 0.01 µM respectively, better than the rest of the series. A structure activity relationship (SAR) of this series has been established based on electronic effects and position of different substituents present on phenyl ring. Molecular docking studies were performed to understand the binding interaction of the compounds. [ABSTRACT FROM AUTHOR]

α -Glucosidase enzyme is a therapeutic target for diabetes mellitus and its inhibitors play a vital role in the treatment of this disease. A new series of aryl-oxadiazole Schiff bases (1 – 18) were synthesized and evaluated for α -glucosidase inhibitory potential. Fifteen compounds 1 – 8 , 11 – 13 , and 15 – 18 showed excellent inhibition with IC 50 values ranging from 0.30 ± 0.2 to 35.1 ± 0.80 µM as compared to the standard inhibitor acarbose (IC 50 = 38.45 ± 0.80 µM), nonetheless, the remaining compounds were found to have moderate activity. Among the series, compounds 7 (IC 50 = 0.30 ± 0.2 μM) with hydroxy groups at phenyl rings on either side of the oxadiazole ring was identified as the most potent inhibitor of α -glucosidase. The molecular docking studies were conducted to understand the binding mode of active inhibitors with the active site of enzyme and results supported the experimental data. [ABSTRACT FROM AUTHOR]

A series of 3,5‐disubstituted‐tetrahydro‐thiadiazine‐2‐thione (1‐16) have been synthesized, characterized by elemental analysis, infrared (IR), UV‐visible, 1H NMR, 13C NMR, and MS spectroscopic techniques, and screened against jack bean urease. Among 16 compounds, compounds (1), (2), (3), (4), (6), (7), and (9) demonstrated excellent urease inhibitory activity with IC50 values (9.8 ± 0.5, 11.0 ± 0.6, 16.0 ± 1.5, 17.2 ± 0.5, 15.4 ± 0.5, 19.7 ± 0.4, and 15.8 ± 0.2μM), respectively, even better than the standard thiourea (IC50 = 21 ± 0.01μM). However, compound (8) shows an almost same level of inhibition (IC50 = 22.9 ± 0.3μM), as like standard. In this work, we reported for the first time urease inhibitory activity of thiadiazine thiones and its molecular docking studies. [ABSTRACT FROM AUTHOR]

Di-n-butyl- (1) and diethyltin(IV) (2) derivatives of 3-methylphenylethanoic acid were synthesized and characterized by elemental analysis, atomic absorption, IR, 1H and 13C NMR spectroscopy and mass spectrometry. The spectroscopic data and single crystal X-ray diffraction studies for complex 2 have confirmed a bidentate coordination mode of the carboxylate ligand and the presence of hexacoordinated tin atoms in the complexes. The complexes were screened for their in vitro antibacterial activity against selected gram positive and gram negative bacterial strains. The anticancer potential was assessed against prostate cancer cell lines. Both complexes have shown higher activities than the ligand acid. Complex 1 with an IC50 value of 4.97 ± 0.27 μg/mL was found to be better anti prostate cancer agent than complex 2 (IC50 = 11.26 ± 2.18 μg/mL). Molecular docking study has suggested antibacterial action of the complexes in terms of their ability to develop hydrogen bonding and hydrophobic interactions with vital residues of the target proteins like tyrosyl-tRNA synthase from Staphylococcus aureus (gram-positive bacteria) and undecaprenyl diphosphate synthase from Escherichia coli (gram-negative bacteria). [ABSTRACT FROM AUTHOR]

Four new diorganotin(IV) carboxylates, [n-Bu2SnL2] (1), [Et2SnL2] (2), [Me2SnL2] (3) and [n-Oct2SnL2] (4), where L = 3-(4-chlorophenyl)-2-methylacrylate, were synthesized and characterized by elemental analysis, FT-IR, multinuclear NMR (1H, 13C, and 119Sn) and X-ray single crystal analysis for 1. A chelating bidentate ligand and six-coordinate tin centers were confirmed in the solid state by IR for all complexes and for 1 by X-ray single crystal analysis. The NMR study has shown a decrease in the coordination number of tin in solution. The complexes were screened for their in vitro antibacterial and antifungal activities. A compromised lipo/hydrophilicity and a diffusion controlled antimicrobial activity was shown by the complexes in the order 1 > 2>3 > 4. Molecular docking studies have shown hydrogen bonding and hydrophobic interactions for 1 with the target proteins of the antimicrobial strains. [ABSTRACT FROM AUTHOR]

The inhibition of Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) enzymes represents a potential target in the treatment of Alzheimer disease. AChE and BChE inhibition was studied by biogenic metal oxide nanoparticles (ZnO, NiO, Fe2O3, Co3O4 and PbO) synthesized using aqueous extracts of Sageretia thea (Osbeck.). The results demonstrated that the highest inhibition was shown by PbO nanoparticles with the IC50 values of 101.9 µg/mL for AChE and 119.8 µg/mL for BChE. Furthermore, the results obtained from molecular docking studies analyzing the interaction of nanoparticles with enzymes, were in good agreement with the experimental data. [ABSTRACT FROM AUTHOR]

Urease is known to be one of the major causes of diseases induced by Helicobacter pylori , thus allow them to survive at low pH inside the stomach and thereby, play an important role in the pathogenesis of gastric and peptic ulcer, apart from cancer as well. Keeping in view the great importance of urease inhibitors, here in this study we have synthesized piperazine derivatives ( 1 – 15 ) and evaluated for their urease inhibitory activity. All analogs showed excellent inhibitory potential with IC 50 values ranging between 1.1 ± 0.01 and 33.40 ± 1.50 µM when compared with the standard inhibitor thiourea (IC 50  = 21.30 ± 1.10 µM). Structure activity relationship has been established for all compounds which are mainly based upon the substitution on phenyl ring. Molecular docking study was performed in order to understand the binding interaction of the compounds in the active site of enzyme. [ABSTRACT FROM AUTHOR]

Dengue virus (DENV) has emerged as a rapidly spreading epidemic throughout the tropical and subtropical regions around the globe. No suitable drug has been designed yet to fight against DENV, therefore, the need for safe and effective antiviral drug has become imperative. The envelope protein of DENV is responsible for mediating the fusion process between viral and host membranes. This work reports an in silico approach to target B and T cell epitopes for dengue envelope protein inhibition. A conserved region “QHGTI” in B and T cell epitopes of dengue envelope glycoprotein was confirmed to be valid for targeting by visualizing its interactions with the host cell membrane TIM-1 protein which acts as a receptor for serotype 2 and 3. A reverse pharmacophore mapping approach was used to generate a seven featured pharmacophore model on the basis of predicted epitope. This pharmacophore model as a 3D query was used to virtually screen a chemical compounds dataset “Chembridge”. A total of 1010 compounds mapped on the developed pharmacophore model. These retrieved hits were subjected to filtering via Lipinski’s rule of five, as a result 442 molecules were shortlisted for further assessment using molecular docking. Finally, 14 hits of different structural properties having interactions with the active site residues of dengue envelope glycoprotein were selected as lead candidates. These structurally diverse lead candidates have strong likelihood to act as further starting structures in the development of novel and potential drugs for the treatment of dengue fever. [ABSTRACT FROM AUTHOR]

Context:Malaria remains one of the prevalent infectious diseases worldwide.Plasmodium falciparum1-deoxy-d-xylulose-5-phosphate reductoisomerase (PfDXR) plays a role in isoprenoid biosynthesis in the malaria parasite, making this parasite enzyme an attractive target for antimalarial drug design. Fosmidomycin is a promising DXR inhibitor, which showed safety as well as efficacy againstPlasmodium falciparummalaria in clinical trials. However, due to its poor oral bioavailability and non-drug-like properties, the focus of medicinal chemists is to develop inhibitors with improved pharmacological properties. Objective:This study described the computational design of new and potent inhibitors for deoxyxylulose 5-phosphate reductoisomerase and the prediction of their pharmacokinetic and pharmacodynamic properties. Material and methods:A complex-based pharmacophore model was generated from the complex X-ray crystallographic structure ofPfDXRusing MOE (Molecular Operating Environment). Furthermore, MOE-Dock was used as docking software to predict the binding modes of hits and target enzyme. Results:Finally, 14 compounds were selected as new and potent inhibitors ofPfDXRon the basis of pharmacophore mapping, docking score, binding energy and binding interactions with the active site residues of the target protein. The predicted pharmacokinetic properties showed improved permeability by efficiently crossing blood–brain barrier. While,in silicopromiscuity binding data revealed that these hits also have the ability to bind with otherP. falciparumdrug targets. Discussion and conclusion:In conclusion, innovative scaffolds with novel modes of action, improved efficacy and acceptable physiochemical/pharmacokinetic properties were computationally identified. [ABSTRACT FROM AUTHOR]

The family Polygonaceae is known for its traditional use in the management of various neurological disorders including Alzheimer's disease (AD). In search of new anti-AD drugs, β-sitosterol isolated from Polygonum hydropiper was subjected to in vitro, in vivo, behavioral and molecular docking studies to confirm its possibility as a potential anti-Alzheimer's agent. The in vitro AChE, BChE inhibitory potentials of β-sitosterol were investigated following Ellman's assay. The antioxidant activity was tested using DPPH, ABTS and H2O2 assays. Behavioral studies were performed on a sub-strain of transgenic mice using shallow water maze (SWM), Y-maze and balance beam tests. β-sitosterol was tested for in vivo inhibitory potentials against cholinesterase's and free radicals in the frontal cortex (FC) and hippocampus (HC). The molecular docking study was performed to predict the binding mode of β-sitosterol in the active sites of AChE and BChE as inhibitor. Considerable in vitro and in vivo cholinesterase inhibitory effects were observed in the β-sitosterol treated groups. β-sitosterol exhibited an IC50 value of 55 and 50 μg/ml against AChE and BChE respectively. Whereas, the activity of these enzymes were significantly low in FC and HC homogenates of transgenic animals. Molecular docking studies also support the binding of β-sitosterol with the target enzyme and further support the in vitro and in vivo results. In the antioxidant assays, the IC50 values were observed as 140, 120 and 280 μg/ml in the DPPH, ABTS and H2O2 assays respectively. The free radicals load in the brain tissues was significantly declined in the β-sitosterol treated animals as compared to the transgenicsaline treated groups. In the memory assessment and coordination tasks including SWM, Y-maze and balance beam tests, β-sitosterol treated transgenic animals showed gradual improvement in working memory, spontaneous alternation behavior and motor coordination. These results conclude that β-sitosterol is a potential compound for the management of memory deficit disorders like AD. [ABSTRACT FROM AUTHOR]

The PIM kinases are a family of serine/threonine kinases that catalyze the ATP dependent phosphorylation. These kinases were identified to be overexpressed in a variety of malignancies and tumors and hence can be taken a therapeutic drug target. Pharmacophore-based virtual screening, were employed to identify lead compounds for PIM kinases. A seven featured pharmacophore model was developed on the basis of tricyclic benzothienopyrimidinone, a triple inhibitor of PIM kinases. The validated pharmacophore model was used to screen ZINC database. As a result, 1028 compounds were mapped on the pharmacophore model. These initial hits, were subjected to filtering via Lipinski's rule of five to predict drug like molecules. 1028 drug like hits were selected for evaluation using docking simulation. Finally, 22 hits having different structural properties and binding modes with all the three PIM kinases were selected as lead candidates for triple inhibitors. These candidates having different scaffolds have a strong likelihood to act as further starting points in the development of new and potential PIM kinases inhibitors. [ABSTRACT FROM AUTHOR]

A series of hydrazones 5a-i were synthesized by the condensation of hydrazides derived from dichlorophenylacetic acids with different aromatic aldehydes and ketones. Their structures were confirmed by spectroscopic data and elemental analysis. Hydrazones 5a-i were evaluated for α-glucosidase and urease inhibition activities. Five compounds exhibited potent α-glucosidase inhibitory potential with IC50 values 8.5 ± 0.3, 22.2 ± 0.78, 32.9 ± 1.5, 34 ± 2.4, and 170.6 ± 7.5 μM, respectively, which are many times better than that of the standard inhibitor acarbose ( IC50 = 840 ± 1.73 μM). Furthermore, molecular docking study was performed to explore the binding mode in the active sites of α-glucosidase and urease enzymes. [ABSTRACT FROM AUTHOR]

A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds 5a, 5d, and 5f were solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds 4a, 4b, 4c, 4d, 4e, 4f, and 4g are potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT), and N-acetylcysteine. Compounds 4a–4e (IC50=101.8±0.8–124.4±4.4 μM) and 4g (IC50=104.1±1.9 μM) were more potent antioxidants than the standard (BHT, IC50=128.8±2.1 μM). The enzyme inhibition potential of these compounds was also evaluated, in vitro, against thymidine phosphorylase, α-glucosidase, and β-glucuronidase enzymes. Compounds 4c, 4h, 4o, 4p, 4q, 5f, and 5m were found to be potent α-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds 4v, and 5h were found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x, 4z, and 5a–5m) were found to be noncytotoxic against human prostate (PC-3), Henrietta Lacks cervical (HeLa) and Michigan Cancer Foundation-7 breast (MCF-7) cancer cell lines, and 3T3 normal fibroblast cell line, except 4y which was cytotoxic against all the cell lines. [ABSTRACT FROM AUTHOR]

The main objective of cancer management with chemotherapy (anticancer drugs) is to kill the neoplastic (cancerous) cell instead of a normal healthy cell. The bioassay-guided isolation of two new sesquiterpene coumarins (compounds 1 and 2) have been carried out from Ferula narthex collected from Chitral, locally known as "Raw." Anticancer activity of crude and all fractions have been carried out to prevent carcinogenesis by using MTT assay. The n-hexane fraction showed good activity with an IC50 value of 5.434 ± 0.249µg/mL, followed by crude MeFn extract 7.317 ± 0.535µg/mL, and CHCl3 fraction 9.613 ± 0.548µg/mL. Compounds 1 and 2 were isolated from chloroform fraction. Among tested pure compounds, compound 1 showed good anticancer activity with IC50 value of 14.074 ± 0.414µg/mL. PASS (Prediction of Activity Spectra) analysis of the compound 1 was carried out, in order to predicts their binding probability with anti-cancer target. As a results the compound 1 showed binding probability with human histone acetyltransferase with Pa (probability to be active) value of 0.303. The compound 1 was docked against human histone acetyltransferase (anti-cancer drug target) by using molecular docking simulations. Molecular docking results showed that compound 1 accommodate well in the anti-cancer drug target. Moreover the activity support cancer chemo preventive activity of different compounds isolated from the genus Ferula, in accordance with the previously reported anticancer activities of the genus. [ABSTRACT FROM AUTHOR]

The synthesis of the new diethyl ammonium salt of diethylammonium(E)-5-(1,5-bis(4- fluorophenyl)-3-oxopent-4-en-1-yl)-1,3-diethyl-4,6-dioxo-2-thioxohexaydropyrimidin-5-ide 3 via a regioselective Michael addition of N,N-diethylthiobarbituric acid 1 to dienone 2 is described. In 3, the carboanion of the thiobarbituric moiety is stabilized by the strong intramolecular electron delocalization with the adjacent carbonyl groups and so the reaction proceeds without any cyclization. The molecular structure investigations of 3 were determined by single-crystal X-ray diffraction as well as DFT computations. The theoretically calculated (DFT/B3LYP) geometry agrees well with the crystallographic data. The effect of fluorine replacement by chlorine atoms on the molecular structure aspects were investigated using DFT methods. Calculated electronic spectra showed a bathochromic shift of the π-π* transition when fluorine is replaced by chlorine. Charge decomposition analyses were performed to study possible interaction between the different fragments in the studied systems. Molecular docking simulations examining the inhibitory nature of the compound show an anti-diabetic activity with Pa (probability of activity) value of 0.229. [ABSTRACT FROM AUTHOR]

This work has described the synthesis of novel class (1 – 25) of benzofuran based hydrazone. The hybrid scaffolds (1 – 25) of benzofuran based hydrazone were evaluated in vitro , for their urease inhibition. All the newly synthesized analogues (1 – 25) were found to illustrate moderate to good urease inhibitory profile ranging from 0.20 ± 0.01 to 36.20 ± 0.70 µM. Among the series, compounds 2 2 (IC 50 = 0.20 ± 0.01 µM), 5 (IC 50 = 0.90 ± 0.01 µM), 23 (IC 50 = 1.10 ± 0.01 µM) and 25 (IC 50 = 1.60 ± 0.01 µM) were found to be the many folds more potent than thiourea as standard inhibitor (IC 50 = 21.86 ± 0.40 µM). The elevated inhibitory profile of these analogues might be due to presence of dihydroxy and flouro groups at different position of phenyl ring B attached to hydrazone skeleton. These dihydroxy and fluoro groups bearing compounds have shown many folds better inhibitory profile through involvement of oxygen of dihydroxy groups in hydrogen bonding with active site of enzymes. Various types of spectroscopic techniques such as 1H-, 13C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed compounds. To find SAR, molecular docking studies were performed to understand, the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data. [ABSTRACT FROM AUTHOR]

In this work, govaniadine, an alkaloid isolated fromCorydalis govanianaWall. was evaluated for its analgesic activity by writhing and hot-plate tests. Govaniadine did not display any toxic effects in mice up to 20 mg/kg during 24 h assessment study. The acetic acid-induced writhing was significantly reduced by pretreatment with govaniadine in a dose-dependent manner (1.25–5.0 mg/kg, intraperitoneally (i.p.)). Furthermore, molecular docking study has shown that this alkaloid binds the COX-2 enzyme. In the hot-plate test, govaniadine at dose of 2.5 and 5 mg/kg, i.p. displayed analgesic effect at all time points (30, 60, 90 and 120 min). The analgesic effect of govaniadine was significantly antagonised by naloxone administration. Our results demonstrate for the first time that the peripheral and central analgesic effects of govaniadine could be in part related to the involvement of COX-2 activity and by its interaction with the opioid system. [ABSTRACT FROM PUBLISHER]

The current study was designed to explore the antinociceptive, antiinflammatory and antipyretic activity of pistagremic acid (PA), isolated from Pistacia integerima bark in various animal paradigms. The results illustrated significant inhibition of noxious stimulation in acetic acid induced writhing test with maximum effect of 68% at 10 mg/kg i.p. In tail immersion test, pretreatment with PA demonstrated marked activity during various assessment times in a dose dependent manner. The maximum pain inhibition was 59.46% at 10 mg/kg i.p. after 90 min of PA treatment. However, the injection of naloxone did not antagonize this induced effect. PA significantly ameliorated post carrageenan induced edema dose dependently during various stages of inflammation. The effect was most dominant (60.02%) after 3 rd h of drug administration when examined for 5 h. Similarly, it provoked dose dependent antipyretic effect in febrile mice with maximum of 60.04% activity at 10 mg/kg i.p. after 3rd hour of PA post treatment. Furthermore, molecular docking was carried out to understand the binding mode of PA. From the docking study it was observed that PA fits well in the active site of COX-2 enzyme due to hydrogen and hydrophobic moiety interactions to the important active site of molecule. In conclusion, PA possesses strong peripheral and central antinociceptive activity independent of opioidergic effect which was augmented by its anti-inflammatory and antipyretic activities. [ABSTRACT FROM AUTHOR]

Context: The three Pim serine/threonine kinases (Pim-1, Pim-2, and Pim-3) belong to a small family of kinases that regulate numerous signaling pathways fundamental to the development of tumors. Pim kinases' overexpression has been reported in numerous solid and hematological tumors and, in particular, prostate cancer (Pim-1). Objectives: This study investigated the binding modes of benzofuran-2-carboxlic acids against Pim-1 kinase, hence providing useful information for the active inhibition of it. Materials and methods: In present study, molecular docking approach via MOE-Dock program was applied to predict the binding interactions of some known Pim-1 kinase inhibitors. First validation of the docking protocol was carried out by calculating RMSD for the co-crystallized and docked ligands. Using the same protocol, all the compounds were docked into the active site of Pim-1 kinase. Results: All the compounds showed significant interactions and good correlation with the experimental data. The results illustrate that compounds with optimum basicity and relevant distance between the acidic and basic groups showed optimum interactions with the active site residues of Pim-1 kinase. Conclusion: We hope that this study will be helpful in designing new, structurally diverse and more potent compounds for the active treatment of prostate cancer and other related diseases caused by deregulation of Pim-1 kinase. [ABSTRACT FROM AUTHOR]

Abstract: Five ursane type sulfated saponins have been isolated from the aerial parts of Zygophyllum fabago Linn. (locally called Chashum). The urease inhibitory effects of these compounds have been investigated for the first time as well as their molecular docking studies have also been carried out to check the structure–activity relationship. The IC50 values of these compounds could not be found due to paucity of the samples. The molecular docking studies were performed only for the most active compound mono sodium salt of 3β,23-di-O-sulfonyl-23-hydroxyurs-20(21)-en-28-oic acid 28-O-[β-d-glucopyranosyl] ester (Zygofaboside A; 1). [Copyright &y& Elsevier]

In continuation of our previous study on the urease inhibition by a number of chalcones, 2,3-dihydro-1,5-benzothiazepines and 2,3,4,5-tetrahydro-1,5-benzothiazepines, FlexX docking has been exploited to get a deeper insight into the mechanism of their inhibitory action. A comparison of the IC50 values of the active compounds reveals that, of the three classes of compounds studied, 2,3-dihydro-1,5-benzothiazepines were the most potent urease inhibitors. An in silico examination of these compounds showed that the activity is related to the interaction of ligand with the nickel metallocentre, its interaction with two amino acid residues, Asp224 and Cys322, in addition to the orientation of rings A and B in the catalytic core of the enzyme. The most active compound 2,3-dihydro-1,5-benzothiazepine (4) anchor tightly through a network of interactions with Ni701 and Ni702. This includes a number of hydrogen bonds and hydrophobic contacts with the amino acid residues in its vicinity. For their reduced analogs, the difference in the activity of different diastereomers has been observed to be configuration-dependent. This may be ascribed mainly to the difference in the orientation of ring B of the two stereoisomers and the extent of their interaction with Asp224 and Cys322 present in the catalytic core of the enzyme. [ABSTRACT FROM AUTHOR]

Ficus benghalensis has been used by local health care practitioners to treat pain, inflammation, rheumatism, and other health issues. In this study, the crude extract and diverse fractions, along with the isolated compound of F. benghalensis were examined for their roles as muscle relaxants, analgesics, and sedatives. The extract and isolated compound 1 were screened for muscle-relaxant, analgesic, and sedative actions. The acetic acid-mediated writhing model was utilized for analgesic assessment, the muscle relaxant potential was quantified through traction and inclined plan tests, and the open field test was applied for sedative effects. The extract/fractions (25, 50, and 100 mg/kg) and isolated compounds (2.5, 5, 10, and 20 mg/kg) were tested at various doses. A profound (p< 0.001) reduce in the acetic acid-mediated writhing model was observed against carpachromene (64.44%), followed by ethyl acetate (60.67%) and methanol (58.42%) fractions. A marked (p< 0.001) muscle relaxant activity was noticed against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Regarding the sedative effect, a significant action was noted against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Furthermore, the binding modes of the isolated compounds were explored using molecular docking. The molecular docking study revealed that the isolated compound possessed good binding affinity for COX2 and GABA. Our isolated compound may possess inhibitory activity against COX2 and GABA receptors. The extract and isolated compounds of Ficus benghalensis can be used as analgesics, muscle relaxants, and sedatives. However, detailed molecular and functional analyses are essential to ascertain their function as muscle relaxants, analgesics, and sedatives. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNF-α) is a drug target in rheumatoid arthritis and several other auto-immune disorders. TNF-α binds with TNF receptors (TNFR), located on the surface of several immunological cells to exert its effect. Hence, the use of inhibitors that can hinder the complex formation of TNF-α/TNFR can be of medicinal significance. In this study, multiple chem-informatics approaches, including descriptor-based screening, 2D-similarity searching, and pharmacophore modelling were applied to screen new TNF-α inhibitors. Subsequently, multiple-docking protocols were used, and four-fold post-docking results were analyzed by consensus approach. After structure-based virtual screening, seventeen compounds were mutually ranked in top-ranked position by all the docking programs. Those identified hits target TNF-α dimer and effectively block TNF-α/TNFR interface. The predicted pharmacokinetics and physiological properties of the selected hits revealed that, out of seventeen, seven compounds (4, 5, 10, 11, 13–15) possessed excellent ADMET profile. These seven compounds plus three more molecules (7, 8 and 9) were chosen for molecular dynamics simulation studies to probe into ligand-induced structural and dynamic behavior of TNF-α, followed by ligand-TNF-α binding free energy calculation using MM-PBSA. The MM-PBSA calculations revealed that compounds 4, 5, 7 and 9 possess highest affinity for TNF-α; 8, 11, 13–15 exhibited moderate affinities, while compound 10 showed weaker binding affinity with TNF-α. This study provides valuable insights to design more potent and selective inhibitors of TNF-α, that will help to treat inflammatory disorders. [ABSTRACT FROM AUTHOR]

Here in this study regarding the over expression of TP, which causes some physical, mental and socio problems like psoriasis, chronic inflammatory disease, tumor angiogenesis and rheumatoid arthritis etc. By this consideration, the inhibition of this enzyme is vital to secure life from serious threats. In connection with this, we have synthesized twenty derivatives of isoquinoline bearing oxadiazole (1–20), characterized through different spectroscopic techniques such as HREI-MS, 1H- NMR and 13C-NMR and evaluated for thymidine phosphorylase inhibition. All analogues showed outstanding inhibitory potential ranging in between 1.10 ± 0.05 to 54.60 ± 1.50 µM. 7-Deazaxanthine (IC50 = 38.68 ± 1.12 µM) was used as a positive control. Through limited structure activity relationships study, it has been observed that the difference in inhibitory activities of screened analogs are mainly affected by different substitutions on phenyl ring. The effective binding interactions of the most active analogs were confirmed through docking study. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Phytosterols including beta-sitosterol and stigmasterol were isolated from Polygonum hydropiper L. • Structures were confirmed via NMR and Mass analysis. • Phytosterols were evaluated against HeLa, MCF-7 and NIH/3T3 cell lines using MTT assays. • Compounds were docked against Tyrosine kinase an important enzyme in the cancer drug targets. Abstract Based on our previous studies on cytotoxic potentials of Polygonum hydropiper L, two steroidal compounds beta-sitosterol and stigmasterol were isolated from the most active fraction and were subjected to cell lines cytotoxicity. Isolated compounds were tested against HeLa, MCF-7 and NIH/3T3 cell lines following MTT assay. Furthermore, the compounds were also docked against tyrosine kinase enzyme to predict the binding mode of phytosterols in the active sites of the enzyme. Beta-sitosterol exhibited considerable cytotoxicity against NIH/3T3, HeLa and MCF-7 cell with 67.05 ± 2.08, 79.63 ± 2.34 and 71.50 ± 1.57% lethality respectively at 1 mg/ml concentration. Median inhibitory concentrations calculated from dose response curve against NIH/3T3, HeLa and MCF-7 cells were 440, 170 and 200 µg/ml respectively. Stigmasterol was more effective against MCF-7 and NIH/3T3 cells by killing 87.50 and 81.45% cancerous cells respectively at 1 mg/ml concentration. Stigmasterol showed 77.25% cyctotoxicity against HeLA cells at 1 mg/ml concentration in MTT assay. The IC 50 values for HeLA, MCF-7 and NIH/3T3 cells were 170, 60 and 140 µg/ml respectively. In docking studies, the docking score for beta-sitosterol and stigmasterol were −7.266 and −4.89 respectively. The binding energies for beta-sitosterol and stigmasterol were −41.21 and −41.04 respectively. Such lower binding energies indicate that the compounds fit into the active site more strongly. Binding affinities for both compounds were −7.76 and −7.68 respectively. Both phytosterols possess significant anticancer potentials and can be effective in the prevention and treatment of several malignancies. [ABSTRACT FROM AUTHOR]

New zinc(II) carboxylate complexes [Zn(3-F-C 6 H 4 CH 2 COO) 2 ] n ( 1 ), [Zn 3 (3-F-C 6 H 4 CH 2 COO) 6 (Phen) 2 ] ( 2 ) and [Zn 3 (3-F-C 6 H 4 CH 2 COO) 6 (bipy) 2 ] ( 3 ) were synthesized and characterized by atomic absorption, single crystal structural analysis and IR studies. Complex 1 crystallizes as a coordination polymer constituting a web of μ − η 1 ,η 1 carboxylate bridged tetrahedral zinc centers. Complexes 2 and 3 comprise trinuclear zinc centers with two terminal fivefold coordinated slightly distorted square-pyramidal and central sixfold coordinated octahedral zinc centers. The complexes were also assessed for their DNA binding ability by UV/− Vis spectroscopy and their behavior rationalized theoretically by molecular docking studies. A DNA binding study has shown groove binding interactions with the complexes. [ABSTRACT FROM AUTHOR]

• Synthesis of substituted quinoline based sulfonohydrazide. • Characterization of synthesized compounds. • Biological activity of synthesized compound as acetylcholinesterase inhibitors. • Biological activity of synthesized compound as butyrylcholinesterase inhibitors. • Structure activity relationship. • Molecular docking studies of potent inhibitors. A series of hydroxy‑quinoline-based sulfonohydrazide derivatives (1–16) were synthesized and their structures were elucidated by using various spectroscopic tools including 1HNMR, 13CNMR and HREI-MS and evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. All synthesized derivatives showed the varied range of AChE and BuChE activities having IC 50 values ranging from 0.20 ± 0.01 to 11.60 ± 0.20 µM (against AChE) and 0.80 ± 0.05 to 22.70 ± 0.30 µM (against BuChE) as compared to standard drug Donepezil (IC 50 = 2.16 ± 0.12 µM & 4.5 ± 0.11 µM, respectively). Among the series, compounds 1, 8, and 10 were identified to be most potent, even more, active than standard drug having IC 50 values of 0.40 ± 0.05, 0.20 ± 0.01, 0.70 ± 0.05 µM (against AChE) and 0.80 ± 0.05, 0.80 ± 0.05, 2.10 ± 0.10 µM (against BuChE) respectively. Based on the substitution pattern around the aryl ring, structure-activity relationship (SAR) analysis was conducted for all synthesized derivatives. Additionally, the molecular docking method was created to investigate the mechanism of interactions between the scaffolds that are most active and the active sites of specific AChE and BuChE enzymes. [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesis of new 1,4-benzodioxin derivatives. • In vitro α -amylase and α -glucosidase, structure enzyme study. • Identification of a new α -amylase and α -glucosidase inhibitors. • Structure activity relationship established. • Molecular docking. Enzyme inhibition is one of the main target for drug development against diabetes mellitus. In this regard we have conducted the synthesis of 1,4-benzodioxin bases Schiff bases (1–25). The α-amylase activities of these compounds (1–25) found in the range of 0.60 ± 0.01 to 19.80 ± 0.40 µM when compared with standard acarbose (12.80 ± 0.10 µM). The α-glucosidase activity ranging from IC 50 = 0.80 ± 0.01 µM to IC 50 = 27.60 ± 0.60 µM when compared with standard acarbose (IC 50 = 12.90 ± 0.10 µM). The structure-activity relationship (SAR) has established for all compounds. The SAR suggest that compounds containing hydroxyl and halogens are active against both enzymes. The molecular docking study was carried out to find the interaction of active compounds with enzymes. Furthermore, ADME property study is also conducted. [ABSTRACT FROM AUTHOR]

Abstract: In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1–18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5–385.9 μM, if compared with the standard acarbose (IC50 = 906 ± 6.387 μM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors. [Copyright &y& Elsevier]

Bisindole analogs 1–17 were synthesized and evaluated for their in vitro β-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50 =1.62±0.04μM), 6 (IC50 =1.86±0.05μM), 10 (IC50 =2.80±0.29μM), 9 (IC50 =3.10±0.28μM), 14 (IC50 =4.30±0.08μM), 2 (IC50 =18.40±0.09μM), 19 (IC50 =19.90±1.05μM), 4 (IC50 =20.90±0.62μM), 7 (IC50 =21.50±0.77μM), and 3 (IC50 =22.30±0.02μM) showed superior β-glucuronidase inhibitory activity than the standard (d-saccharic acid 1,4-lactone, IC50 =48.40±1.25μM). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent β-glucouronidase inhibitors. [ABSTRACT FROM AUTHOR]

• A novel series of benzimidazole derivatives was successfully synthesized. • The benzimidazoles were effectively synthesized by a rapid 'onepot' nitro reductive cyclization reaction using sodium dithionite as reagent. • The compounds were evaluated for their in vitro inhibitory activity against α -amylase and α -glucosidase, as well as their antioxidant properties. • Moreover, the kinetics studies revealed highly favorable binding energies and a. competitive inhibition mode. • Molecular docking studies were conducted to determine the binding mode of the most potent inhibitor. We synthesized a novel 6-(4-substitue-piperazin-1-yl)-2-aryl-1 H -benzimidazole derivatives starting from 5-(4-substitue-piperazin-1-yl)-2-nitroaniline with different aldehydes. A quick "onepot" nitro reductive cyclization synthesis employing sodium hydrosulfite as a reagent produced the benzimidazoles efficiently. Moreover, we carried out in vitro evaluations, which included an investigation of their α-amylase and α-glucosidase inhibitory activities, as well as their antioxidant properties. The results demonstrated that all the synthesized analogs exhibited significant inhibition of both α -glucosidase and α -amylase potential between IC 50 = 0.85 ± 0.25 - 29.72 ± 0.17 µ M and IC 50 = 4.75 ± 0.24 - 40.24 ± 0.10 µ M, respectively, in comparison to the standard acarbose (IC 50 = 14.70 ± 0.11 μ M). According to the analysis of the kinetic experiments, most of active compounds inhibit a competitive mechanism. Furthermore, the synthesized analogs showed notable DPPH radical scavenging capabilities against standard butylated hydroxytoluene, with SC 50 values ranging from 19.05 ± 0.21 to 80.55 ± 0.45 μM. Additionally, molecular docking experiments revealed the interaction profile of each drug when assessing their dock scores to obtain insight into how each chemical would bind to the α -glucosidase and α -amylase enzymes. [Display omitted] [ABSTRACT FROM AUTHOR]