Synthesis Inhibitory Activity Research Articles

Green Synthesis, Anti-cancer and Corrosion Inhibition Activity of Cr2O3 Nanoparticles

The present study deals with the synthesis of Cr2O3nanoparticles (NPs) using Cannabis sativa leaves extract and to assess anti biochemical cancer and corrosion inhibitory activity. The formation of nanoparticles was established by spectrophotometer (UV-vis) at a wavelength of 425 nm while it was kept for one month at room temperature for stability checking. Dynamic Light Scattering analysis revealed the formation of stable Cr2O3 NPs measuring 85-90 nm in diameter. Furthermore, Cr2O3 NPs and Cannabis sativa leaves extract were checked for anti-cancer activity in HepG2 cell lines. The recorded percent cell viability of HepG2 was 64.10 at a minimum concentration (0.01 ppm), whereas at a maximum concentration (10 ppm) it was reduced to 47.25 % after 12 hrs. Further, at 24 hrs, it was reduced up to 21 % and 34.45 % at a minimum and maximum concentrations, respectively. Hence, green synthesized Cr2O3 NPs possessed promising anti-cancer activity. Loss in weight method is used to evaluate the corrosion inhibition activity on mild steel in 0.5 M HCl, HNO3, and NH3 solutions. The value of IE also increases with increasing the concentration of Cr2O3 NPs. It is clear that in basic (NH3) medium, Cr2O3 NPs show the highest inhibition performance of about 89%, and in an acidic medium, it was80%at 1.0 g/l concentration. The concentration of Cr2O3 NPs increases with a decrease in the rate of corrosion, which confirmed an increase in the efficiency of inhibition.

New ribosome-inactivating proteins and other proteins with protein synthesis-inhibiting activities.

Ribosome-inactivating proteins (RIPs) consist of three varieties. Type 1 RIPs are single-chained and approximately 30-kDa in molecular weight. Type 2 RIPs are double-chained and composed of a type 1 RIP chain and a lectin chain. Type III RIPs, such as maize b-32 barley and JIP60 which are produced as single-domain proenzymes, possess an N-terminal domain corresponding to the A domain of RIPs and fused to a C-terminal domain. In addition to the aforementioned three types of RIPs originating from flowering plants, there are recently discovered proteins and peptides with ribosome-inactivating and protein synthesis inhibitory activities but which are endowed with characteristics such as molecular weights distinctive from those of the regular RIPs. These new/unusual RIPs discussed in the present review encompass metazoan RIPs from Anopheles and Culex mosquitos, antimicrobial peptides derived from RIP of the pokeweed Phytolacca dioica, maize RIP (a type III RIP derived from a precursor form), RIPs from the garden pea and the kelp. In addition, RIPs with a molecular weight smaller than those of regular type 1 RIPs are produced by plants in the Cucurbitaceae family including the bitter gourd, bottle gourd, sponge gourd, ridge gourd, wax gourd, hairy gourd, pumpkin, and Chinese cucumber. A small type II RIP from camphor tree (Cinnamomum camphora) seeds and a snake gourd type II RIP with its catalytic chain cleaved into two have been reported. RIPs produced from mushrooms including the golden needle mushroom, king tuber mushroom, straw mushroom, and puffball mushroom are also discussed in addition to a type II RIP from the mushroom Polyporus umbellatus. Bacterial (Spiroplasma) RIPs associated with the fruitfly, Shiga toxin, and Streptomyces coelicolor RIP are also dealt with. The aforementioned proteins display a diversity of molecular weights, amino acid sequences, and mechanisms of action. Some of them are endowed with exploitable antipathogenic activities.

Synthesis, antimicrobial and chitinase inhibitory activities of 3-amidocoumarins.

A series of 3-amidocoumarins has been synthesized and tested in vitro for their anitimicrobial and chitinase inhibitory activities. Among these, compounds 5k, 5l, 8b-8d, 8f and 8g exhibited good antibacterial activity with MIC values in the range of 6.25-25µg/mL against some of the tested strains while compounds 5l, 8b, 8c and 8f showed good activity against at least one or two fungal strains. Some of the assayed compounds 5d, 5k, 5l, 8b and 8c displayed significant chitinase inhibitory activity with IC50 values in the range of 3.74-5.6µM. Among them, 5l proved to be potent chitinase inhibitor with IC50 value of 3.74µM. To better understand the enzyme-inhibitor interactions molecular docking study of all the synthesized compounds was carried out on Aspergillus fumigatus chitinase 1W9U. The compound 5l showed high binding affinity with the receptor with binding energy value of -8.44 Kcal/mol. This study also provides structure activity relationship (SAR) of synthesized compounds.

Facile one-pot synthesis, butyrylcholinesterase and α-glucosidase inhibitory activities, structure–activity relationship, molecular docking and DNA–drug binding analysis of Meldrum’s acid derivatives

Meldrum’s acid derivatives were facile synthesized by one-pot condensation process and characterized by NMR (1H, 13C, DEPT-90 and DEPT-135) and EI-MS. The synthesized compounds were screened for their potential to inhibit butyrylcholinesterase (BChE) and α-glucosidase enzymes. Interestingly, the derivative 3a showed potent α-glucosidase inhibitory activity, with the IC50 value equal to 2.1 mg/mL as compared to standard acarbose (IC50 = 4.7 mg/mL), whereas, in terms of BChE inhibitory activity investigation, the derivatives 3a and 3c showed novel results, with the IC50 values equal to 1.2 and 2.9 mg/mL, respectively, as compared to standard galantamine hydrobromide (IC50 = 4.7 mg/mL), making derivative 3a a dual inhibitor of both enzymes. Further, structure–activity relationship, comparative molecular docking analysis and the DNA–drug binding interaction were studied to investigate relationship between the chemical structure and its biological activity, inhibition of mechanism, interaction of compounds, DNA binding constant and Gibbs free energy. Structural insights into inhibitor binding to the α-glucosidase and BuChE revealed significant contribution of hydrophobic regions and significant residues of active sites. Comparative molecular docking studies showed that the residues of oxyanion hole, catalytic triad and hydrophobic pocket were actively engaged in interaction with the inhibitor. DNA binding constant was found in the order Kb 3e > Kb 3c > Kb 3a > Kb 3b > Kb 3d, while Gibbs free energy was found in the order ∆G 3e > ∆G 3a > ∆G 3b > ∆G 3c > ∆G 3d.

Synthesis and urease inhibitory activity of 1,4-benzodioxane-based thiosemicarbazones: Biochemical and computational approach

The hyperactivity of urease enzyme is associated with clinically important complications including stomach ulcers and kidney stones. This enzyme provides a suitable environment to Helicobacter pylori at low pH in the stomach, a causative agent of peptic and ulcer gastric that may lead to cancer. Natural and synthetic small molecules were reported to inhibit urease enzyme. Within this context, a new series of 1,4-benzodioxane-based thiosemicarbazones (3a-p) were synthesized and screened in vitro against urease enzyme to elucidate their anti-urease activity. All the compounds displayed potent inhibitory potential with IC50 values ranging between 3.65 ± 2.64 to 31.9 ± 1.094 μM, under positive control of thiourea (IC50 = 20.8 ± 0.75 μM). Structural activity relationship (SAR) has revealed a variation based on substituents pattern at R group. The results of docking study suggest that these compounds thermodynamically binds via nickel atoms present in the active-site of urease. The in silico docking analysis and our experimental findings are in excellent co-relation. The pharmacokinetic behavior of all the compounds were also predicted.

Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives

Synthesis and Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Evaluation of Novel Carbazole-Based Carbohydrazone Derivatives

Synthesis, Crystal Structure and Neuraminidase Inhibitory Activity of 1,2,4-Triazole-3-sulfide Derivatives

Synthesis, Crystal Structure and Neuraminidase Inhibitory Activity of 1,2,4-Triazole-3-sulfide Derivatives

The Synthesis and Glycosidase Inhibitory Activity of Analogues of Tiruchanduramine

The Synthesis and Glycosidase Inhibitory Activity of Analogues of Tiruchanduramine

Chemical synthesis of a haemathrin sulfoprotein library reveals enhanced thrombin inhibition following tyrosine sulfation

The synthesis and thrombin inhibitory activity of eight homogeneously sulfated variants of the haemathrin proteins from tick saliva is described.

Synthesis and AChE inhibitory activity of N-glycosyl benzofuran derivatives

AbstractSix N-glycosyl benzofuran derivatives were synthesized by the catalysis of organic bases and condensation agents. The benzofuran derivatives were obtained by the reaction of various salicylaldehydes in acetone, and then hydrolyzed to the corresponding carboxylic acids. Finally, the target compounds were synthesized by acylation and the reaction conditions were optimized. The acetylcholinesterase (AChE) inhibitory activity of the desired compounds was tested using Ellman’s method. Most of the compounds showed acetylcholinesterase-inhibition activity; N-(2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl)benzofuran-2-carbxamide (5a) showed the best acetylcholinesterase inhibition, with an inhibitory rate of 84%.

Synthesis and cholinesterase inhibitory activity studies of some piperidinone derivatives

Synthesis and cholinesterase inhibitory activity studies of some piperidinone derivatives

Synthesis and PTP Inhibitory Activity of Illudalic Acid and Its Methyl Ether, with Insights into Selectivity for LAR PTP over Other Tyrosine Phosphatases under Physiologically Relevant Conditions.

The protein tyrosine phosphatase (PTP) family of enzymes includes many attractive therapeutic targets, such as those in the leukocyte common antigen-related (LAR) subfamily of receptor PTPs. Synthesis and PTP inhibitory activity of illudalic acid and its methyl ether are described, with a focus on selective inhibition of LAR PTP relative to a small collection of other representative PTPs. The synthesis comprises 16 steps and provides illudalic acid in up to 12% overall yield from neopentylene-fused benzoate 1 (20 steps from commercial materials). Illudalic acid dose-dependently (measured IC50 = 2.1 ± 0.2 μM) and time-dependently inhibits LAR consistent with previous reports of covalent binding. The kinetics of LAR inhibition by illudalic acid are consistent with a two-step mechanism in which the inhibitor and enzyme first interact noncovalently (KI = 130 ± 50 μM), followed by covalent ligation at a rate kinact = 1.3 ± 0.4 min-1. The kinact/KI ratio of 104 corresponds to a t∞1/2 of 0.5 min, as discussed herein. The phenol methyl ether of illudalic acid was found to be less potent in our dose-response assays (measured IC50 = 55 ± 6 μM) but more selective for LAR, with a weaker initial noncovalent interaction and faster covalent ligation of LAR as compared to illudalic acid itself. A truncated analogue of illudalic acid that lacks the neopentylene ring fusion was found to be devoid of significant activity under our assay conditions, in contrast to previous reports. These observations collectively help inform further development of illudalic acid analogues as potent and selective inhibitors of the LAR subfamily of tyrosine phosphatases.

Synthesis, X-Rays Analysis, Docking Study and Cholinesterase Inhibition Activity of 2,3-dihydroquinazolin-4(1H)-one Derivatives

In search of potent cholinesterase inhibitors, we have carried out the synthesis and biologically evaluation of various benzaldehyde based 2,3-dihydroquinazolin-4(1H)-one derivatives. In vitro assay results revealed that all the synthesized compounds showed activity against both enzymes (AChE and BChE) and in few cases, the inhibition activity was even higher than or comparable to the standard drug galantamine. Overall, compounds having chloro or methoxy group attached to the para position of benzaldehyde resulted in potent cholinesterase inhibitors. Within the series, Bromo derivatives 4a-i were more active than their un-substituted counterparts. Amongst all, compound 4c (6,8-dibromo-2-(3-bromo-4-chloro-phenyl)-2,3-dihydro-1H-quinazolin-4-one) with selectivity index of 3.7 for AChE, displayed IC50 values of 3.7±1.05 µM (AChE) and 13.7±0.64 µM (BChE) and can be considered as potential lead compound with a feature of dual cholinesterase (AChE/BChE) inhibition. Insight into the mechanism of inhibition of the synthesized compounds was provided by computed binding modes in the active site of AChE and BChE. Docking study on both isomers of the quinazoline also supported in vitro assay results. Preliminary in silico studies by using online admetSAR server showed that all compounds possessed good pharmacokinetic profile except nitro and methoxy substituted derivatives which were predicted to exhibit AMES toxicity. The synthesized compounds can be used as a structural foundation for the preparation of new potent cholinesterase inhibitors.

Synthesis and Enzyme Inhibitory Activity of Novel Pyridine-2,6-dicarboxamides Bearing Primary Sulfonamide Groups

New pyridine-2,6-dicarboxamide derivatives containing sulfonamide groups were synthesized by the coupling of pyridine-2,6-dicarbonyl dichloride and various aminobenzenesulfonamides in a mixture of dichloromethane and acetone. The pyridinedicarboxamide-based sulfonamides were evaluated as carbonic anhydrase (CA) and cholinesterase (ChE) inhibitors, and they showed IC50 values in the ranges 12.8–37.6 nM against human carbonic anhydrase I (hCA I), 17.8–46.7 nM against human carbonic anhydrase II (hCA II), 98.4–197.5 nM against acetylcholinesterase (AChE), and 82.2–172.7 nM against butyrylcholinesterase (BuChE). These results are comparable with those for known inhibitors such as acetazolamide (IC50 = 32.1 nM for hCA I and IC50 = 51.0 nM for hCA II) and rivastigmine (IC50 = 60.2 nM for AChE and IC50 = 14.0 nM for BuChE), which qualifies the synthesized compounds as candidates for a more in-depth study.

Design, synthesis and cholinesterase inhibitory activity of novel spiropyrrolidine tethered imidazole heterocyclic hybrids

A small library of structurally fascinating spiropyrrolidine tethered imidazole heterocylic hybrids has been synthesized regioselectively in good yields employing [bmim]Br mediated 1,3-diplar cycloaddition strategy. The new class of azomethine ylide generated in situ from l-histidine and 11H-indeno[1,2-b]quinoxalin-11-one reacts with various substituted β-nitrostyrenes affording the spiropyrrolidine tethered imidazole heterocylic hybrids. Compounds thus synthesized were assessed for their in vitro cholinesterase (ChEs) inhibitory activities, among them compounds possessing 4-methyl and 4-methoxy substituents on the aryl ring showed potent activities with IC50 values of 2.02 ± 0.05 and 2.05 ± 0.06 μM against AChE and 12.40 ± 0.14 and 11.45 ± 0.28 μM against BChE enzyme, respectively. In addition, the most active compounds were performed for their molecular docking simulation and the results revealed interesting binding templates to the active site channel of cholinesterase enzymes.

Synthesis, Structural Studies, and α-Glucosidase Inhibitory, Antidiabetic, and Antioxidant Activities of 2,3-Dihydroquinazolin-4(1H)-ones Derived from Pyrazol-4-carbaldehyde and Anilines.

A series of new quinazoline derivatives were designed and synthesized via a one-pot condensation reaction between isatoic anhydride and aromatic aldehydes with anilines using aluminum sulfate as a catalyst in refluxing ethanol. Their structures were confirmed by their physical, IR, 1H NMR, 13C NMR, and mass spectroscopy data and evaluated for some biological effects, including the antioxidant and α-glucosidase inhibitory activities as well as some in vivo hematological parameters. The ability of synthesized compounds in the inhibition of α-glucosidase was also investigated through the in silico study. The significant and important changes in some hematological tests were perceived. Notably, compound 4h showed more reducing effects on cholesterol and triglyceride levels. This molecule certainly has the potential to be developed as the antihyperlipemic compound. The tested compounds, in particular, compounds 4j and 4l, were found to be uniquely reducing blood sugar levels. The entire synthesized compounds showed the potent α-glucosidase inhibitory activity compared with acarbose as a standard material. Amongst, the compounds 4h and 4i showed the strongest enzyme inhibitory potentials than the standard drug acarbose. There was a good correlation between in vitro and in silico studies for ligands 4i and 4l. The majority of compounds presented a good radical scavenging activity, though the compound 4j exhibited the strongest activity, even to the standard of ascorbic acid. Further studies are required to determine whether these main compounds could be a potential treatment for diabetes and hyperlipidemia diseases.

Synthesis and Pancreatic Lipase Inhibitory Activity of Phenacyl Esters of N-Aroyl Amino Acids

Background:Obesity has become a major life-threatening disorder as it is associated with many risk factors such as coronary heart disease, hypertension, type II diabetes and certain forms of cancer. Pancreatic lipase inhibition is one of the alternate strategies to treat obesity. In our previous study, phenacyl ester of N-sulphonyl beta alanine was obtained as a hit molecule when pharmacophore- based virtual screening was carried out using reported pancreatic lipase inhibitors.Objective:In search of novel pancreatic lipase inhibitors, three series of phenacyl esters of Nsubstituted amino acids were synthesized and evaluated for their pancreatic lipase inhibitory activity.Methods:N-aroylation of amino acids and subsequent esterification with different phenacyl bromides in the presence of N,N-Dimethylformamide (DMF) afforded the corresponding phenacyl esters in quantitative yields.Results:The synthesized compounds were found to have good pancreatic lipase inhibitory activity and showed IC50 in the range of 0.036 and 84 μg/ml.Conclusion:All the synthesized compounds showed better pancreatic lipase inhibitory activity and it indicates that the N-aroylated phenacyl esters could be considered as lead moiety for further studies to develop novel anti-obesity potentials.

Synthesis, molecular structure, anti-microbial, anti-oxidant and enzyme inhibition activities of 2-amino-6-methylbenzothiazole and its Cu(II) and Ag(I) complexes

Molecular structure of 2-amin-6-methylbenzothiazole, 1 and its coordination complexes with Ag(I) and Cu(II) were determined by X-ray diffraction. The ligand 2-amin-6-methylbenzothiazole (hereafter represented as L in general formula of complexes) and [AgL2]NO3 crystallize in orthorhombic crystal systems and CuL2(OAc)2 complex is monoclinic. Ligand and its Ag(I) complex possess space groups Pbcn and Cu(II) complex has a space group P21/c. Complex bis(2-amino-6-methylbenzothiazole)diacetatocopper(II), 2 and bis(2-amino-6-methylbenzothiazole)silver(I) nitrate, 3 were obtained by reacting ligand with respective metal salt in a molar ratio 2:1, respectively. The coordination environment of copper metal is octahedral where acetate acts as bidentate ligand and 2-amino-6-methylbenzothiazole occupies trans position with respect to each other. The ligand contains three possible coordination sites (endocyclic nitrogen, exocyclic nitrogen and sulphur). Among three nucleophilic centers the endocyclic nitrogen is more basic and readily coordinates to the metal ion (both Cu and Ag). Nitrate group plays an important role in stabilizing the supramolecular structure of Ag complex wherein NO…H2N- interactions are very effective. Non-covalent interactions in molecules make them efficient medicines. On the basis of certain secondary interactions, compounds 1–3 were expected to be biologically active and were studied as antibacterial, antifungal, antioxidant agents and enzyme inhibitors. Moderate activities against selected strains were observed for the ligand and its complexes. It was observed that the antibacterial and antifungal potentials of the ligand were enhanced by complexation with copper(II) and silver(I) metal ions.

Galloyl esters of trans-stilbenes are inhibitors of FASN with anticancer activity on non-small cell lung cancer cells

Fatty acid synthase (FASN) is a lipogenic enzyme that is selectively upregulated in malignant cells. There is growing consensus on the oncogenicity of FASN-driven lipogenesis and the potential of FASN as a druggable target in cancer. Here, we report the synthesis and FASN inhibitory activities of two novel galloyl esters of trans-stilbene EC1 and EC5. Inhibition of FASN was accompanied by a loss in AKT activation and profound apoptosis in several non-small cell lung cancer (NSCLC) cells at the growth inhibitory concentrations of EC1 and EC5. Both FASN and phospho-AKT levels were concurrently downregulated. However, addition of a lipid concentrate to the treated cells reinstated cell viability and reversed the loss of FASN and AKT protein levels, thus recapitulating the causal relationship between FASN inhibition and the loss in cell viability.

Synthesis and Cholinesterase Inhibitory Activity of N-Phosphorylated/ N-Tiophosphorylated Tacrine.

Alzheimer's disease (AD) is progressive and irreversible neurodegenerative disorder. Current pharmacotherapy is not able to stop progression of the disease and can only improve cognitive functions. Therefore, new drugs are being sought that will slow down the development of the disease. Novel phosphorus and thiophosphorus tacrine derivatives 7-14 were designed, synthesized and their biological activity and molecular modeling was investigated as a new potential anti- Alzheimer's disease (AD) agents. 9-Chlorotacrine was treated with propane-1,3-diamine in the presence of sodium iodide to yield N1-(1,2,3,4-tetrahydroacridin-9-yl)propane-1,3-diamine 6. Finally, it was treated with corresponding acid ester or thioester to give phosphorus or thiophosphorus tacrine derivative 7-14. All of the obtained final structures were characterized by 1H NMR, 13C NMR, 31P NMR and MS. The results of the docking studies showed that the newly designed phosphorus and thiophosphorus tacrine analogs, theoretically possess AChE and BChE-binding ability. Kinetic study showed that 8 and 12 in the series proved to be more potent electric eel AChE (eeAChE) and human (hAChE) inhibitors than tacrine, where 8 inhibited eeAChE three times more than the referenced drug. The highest BChE inhibition revealed 11 and 13. The most active compounds against eeAChE, hAChE and BChE showed mixed type of inhibition. All new synthesized compound exhibited lower toxicity against neuroblastoma.cell line (SH-SY5Y) in comparison with tacrine. Two analogues in the series, 7 and 9, demonstrated lack of cytotoxicity against hepatocellular cells (hepG2).