Anti-urease Activity Research Articles

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.

Microwave and ultrasound promoted greener synthesis of thiazolyl-pyrazoline derivatives and investigation of their biological activities

Six thiazolyl-pyrazoline derivatives were synthesized starting from corresponding chalcone compounds for their antioxidant capacity and antiurease inhibitory activities. In addition to the conventional method, ultrasonic sonication and microwave irradiation methods which are environmental methods were used in the synthesis stage. Compound 2-(5-(3-bromophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-phenyl thiazole (5a) exhibited the most potent antiurease activity with IC50 of 2,28±0,02, which was comparable to the positive control.

Synthesis, DFT calculations, biological investigation, molecular docking studies of β-lactam derivatives

In this study β-lactam derivatives which include 1,3,4-thiadiazole and 1,3,4-oxadiazole structure (8a,b) have been achieved by cyclocondensation reaction. The synthesized compounds were investigated for antioxidant capacity and in vitro antiurease activity. The obtained compounds displayed good-moderate urease inhibiton results in comparison with thiourea, standard drug. Also, frontier molecular orbital analysis, reactivity descriptors (such as ionization energy (I), electron affinity(A), electro negativity(χ), chemical hardnesses (η) and chemical softness (S), chemical potential (μ) and global electrophilicity index (ω)), nonlinear optical properties (NLO) and molecular electrostatic potential (MEP) studied with DFT approach and B3LYP/6–311++G (d,p) level of theory. Nonlinear optical calculations presented that 7b and 8b have very large nonlinear optical activity. In addition, molecular docking studies were performed.

Electronic aspects of hydrogen bond patterns of P=O···H in crystal structures of phosphoramido acid derivatives: QSAR study of anti-urease activity, Hirshfeld surface analysis, and DFT calculations

New derivatives of phosphoramido acid with the formula(C6H11NCH3)(NHCOCF3)P(O)(O−)(CH3–+NH2–C6H11)(1) (amidophosphoricacid), (C6H5)2P(O)(O−)(+NH3–C6H4–NH2)(2) (phosphonicacid), (C6H5O)2P(O)(O−)(+NH3–C6H4–NH2) (3) (phosphoricacidester) were synthesized and characterized by X-ray crystallography. The asymmetric unit of compounds 1–3 consists of one molecule with the P atom in a tetrahedral environment. The X-ray structural analysis showed that the H-bond patterns depend on the kind of atoms linked to the P atom. In the crystal packing of compound 1, P(O)···H–N and C(O)···H–N hydrogen bonds in 3 and P(O)···H–N distances in compounds 2 and 3 led to a one-dimensional arrangement. The energy of P–O···H–N hydrogen bond (EHB) model and stabilizing energies (E2) were calculated. Hirshfeld surface analysis demonstrated that the C···H contact is attributed to CH···π contact in the 2 and 3 compounds and the F···H contact is referred to hydrogen bond in one O···H counterion interaction. Quantitative structure–activity relationship (QSAR) was used to comprehend the relationship between molecular structural features and the inhibitory of investigated compounds. The use of density functional theory along with the QSAR model for enzymes revealed the importance of QH parameter in describing the anti-AChE and anti-urease activities of monophosphoramidates including P(O)–NH2 moiety.

Evaluation of in vitro biological activities of three Hypericum species (H. calycinum, H. confertum, and H. perforatum) from Turkey

Hypericum species have been used since ancient times for medicinal purposes due to their important pharmacological properties. As the most abundant species of the genus Hypericum, Hypericum perforatum is unquestionably one of the best-known and most consumed medicinal plants in the world. The aim of this current study is to evaluate antioxidant, anticholinesterase, and antiurease activities of the methanol extracts of flowering aerial parts of Hypericum calycinum L. Hypericum confertum Choisy, and Hypericum perforatum L. from Turkey. In this study, total phenolic and total flavonoid contents were determined as pyrocatechol and quercetin equivalents, respectively. Antioxidant activities of the species were carried out by using DPPH free radical scavenging, ABTS cation radical scavenging, metal chelate, and CUPRAC activity methods.Among the species that were investigated, it was determined that H. calycinum had the highest total phenolic content (141.12±2.40 μg PEs/mg), whereas H. confertum had the highest total flavonoid content (70.61±0.51 μg QEs/mg). The biochemical results in this study showed that all three species exerted strong antioxidant activity. H. calycinum appeared the most active in all antioxidant activity assays which is mainly due to its rich phenolic content. Additionally, H. calycinum showed the highest acetylcholinesterase inhibitory activity, while H. perforatum had the best inhibition towards butyrylcholinesterase. According to the urease inhibitory activity assay results, only H. calycinum showed low antiurease activity, whereas the other species did not show any activity against urease. The obtained results suggest that the studied three Hypericum species, especially H. calycinum could be promising sources for the treatment of several diseases because of their antioxidant and anticholinesterase properties.

The in vitro and in vivo investigation of biological activities and phenolic analysis of Helichrysum plicatum subsp. plicatum

In Turkey, Helichrysum genus is represented by 26 taxa belonging to 20 species in Turkish flora of which 14 ones are endemic to Turkey. The aerial parts of Helichrysum plicatum subsp. plicatum are used kidney stones, kidney and stomach ailments. The extraction procedures and solvents are important step in processing of bioactive constituents from the plant materials. Therefore, the aim of this study was to evaluate in vitro antioxidant, antimicrobial, anti-urease, anticholinesterase and in vivo anti-inflammatory activities of Helichrysum plicatum subsp. plicatum different extracts. In addition, the phenolic characterization of the Soxhlet and maceration methanol extracts which showed significant antioxidant, anti-urease, antimicrobial, anti-inflammatory and anticholinesterase activities were performed by HPLC-DAD and LC-MS/MS. In the present study, the Soxhlet methanol extract exhibited strong antioxidant, antimicrobial and anticholinesterase activities than other extracts. The maceration methanol extract showed the strongest anti-urease activity. The Soxhlet methanol and maceration methanol extracts showed in vivo anti-inflammatory activities very close to each other. As a result of this study, chlorogenic acid, dicaffeoylquinic acid, luteolin, luteolin-7-O-glucoside, naringenin-O-hexoside and isoquercitrin compounds were analysed in plant. Therefore, it is thought that methanol extracts can be used as a natural source in the future for food and pharmaceutical industries.

Anti-urease, total phenolic content and antioxidant activities of some Inula l. (Asteraceae) taxa in Turkey

The genus Inula belongs to family Asteraceae and it is medicinally important because it possesses cytotoxic, anticancer, hepatoprotective, antibacterial and anti-inflammatory properties. The aim of this research was to explore antioxidant and anti-urease activities of fifteen Inula taxa in Turkey. Ethanol extracts of Inula taxa were obtained by Soxhlet extraction. Antioxidant activity was determined through total antioxidant activity, total phenolic content and copper reducing antioxidant capacity (CUPRAC) analyses. The highest total phenolic content and total antioxidant capacity were found in I. orientalis (158.54?0.002 ?g GAE/mL) and I. macrocephala (189.16?0.002 ?g AAE/mL). CUPRAC activity increases with the increasing concentration of the extracts and the standard. Moreover, all the tested plants exhibited better anti-urease activity than standard thiourea except for I. anatolica and I. thapsoides subsp. thapsoides. Results obtained from this study demonstrate that Inula species might be utilized as a probable natural source in the pharmaceutical and food industries but further and more specific studies are needed to determine active antioxidative and anti-urease compounds in the extracts.

Enzyme inhibition and antibacterial potential of 4-Hydroxycoumarin derivatives

The 4-Hydroxycoumarin derivatives are known to show a broad spectrum of pharmacological applications. In this paper we are reporting the synthesis of a new series of 4-Hydroxycoumarin derivatives synthesized through Knovenegal condensation; they were characterized by using UV-Vis, FT-IR, NMR spectroscopies. The synthesized compounds were evaluated for antibacterial activity against Staphylococcus aureus and Salmonella typhimurium strains. The compounds (2), (3) and (8) showed favorable antibacterial activity with zone of inhibitions 26.5± 0.84, 26.0 ± 0.56 and 26.0 ± 0.26 against Staphylococcus aureus (Gram-positive) respectively. However, the compounds (5) and (9) were found more active with 19.5 ± 0.59 and 19.5 ± 0.32 zone of inhibitions against Salmonella typhimurium (Gram-negative). Whereas, in urease inhibition assay, none of the synthesized derivatives showed significant anti-urease activity; although, in carbonic anhydrase-II inhibition assay, the compound (2) and (6) showed enzyme inhibition activity with IC50 values 263±0.3 and 456±0.1, respectively.

Synthesis, Characterization, Molecular Docking and Enzyme Inhibition Studies of Some Novel Enaminone Derivatives and Their Complexes with Cu(II), Cd(II) and Co(II) Ions

Two new enaminone ligands, 3-chloro-4-{(4-chlorophenyl)amino}pent-3-en-2-one (Ac-PCA), 4-(benzylamino)-3-chloropent-3-en-2-one (Ac-BA) and their metal complexes with transition metal ions [Cu(II), Cd(II) and Co(II)] were prepared and subsequently characterized by FTIR, ICP-AES, UV-Vis, TGA, 1H NMR, 13C NMR and FAB-MS. These newly synthesized compounds were further investigated for anti-acetylcholinesterase (AChE) and anti-urease activities. The (Ac-BA)Cu(II) complex exhibited good anti-AChE while (Ac-BA)2Co(II) complex was potent against anti-urease activities. Other ligands and complexes showed poor to no enzyme inhibitory activities. The synthesized compounds were docked inside acetylcholinesterase enzymes to determine their putative binding mode.

Synthesis, Characterization, Molecular Docking and Enzyme Inhibition Studies of Some Novel Enaminone Derivatives and Their Complexes with Cu(II), Cd(II) and Co(II) Ions

Two new enaminone ligands, 3-chloro-4-{(4-chlorophenyl)amino}pent-3-en-2-one (Ac-PCA), 4-(benzylamino)-3-chloropent-3-en-2-one (Ac-BA) and their metal complexes with transition metal ions were prepared and subsequently characterized by FTIR, ICP-AES, UV-Vis, TGA, 1H NMR, 13C NMR and FAB-MS. These newly synthesized compounds were further investigated for anti-acetylcholinesterase (AChE) and anti-urease activities. The (Ac-BA)Cu(II) complex exhibited good anti-AChE while (Ac-BA)2Co(II) complex was potent against anti-urease activities. Other ligands and complexes showed poor to no enzyme inhibitory activities. The synthesized compounds were docked inside acetylcholinesterase enzymes to determine their putative binding mode. Keywords: Antiureas activity, enaminone, metal complexes, acetylcholinesterase inhibition studies

Effect of patchouli alcohol on macrophage mediated Helicobacter pylori digestion based on intracellular urease inhibition

BackgroundHelicobacter pylori infects almost half of the world population and is listed as a type I carcinoma factor since 1994. Pogostemon cablin (Blanco) Benth. (Labiatae) has been used to treat gastro-intestinal diseases for thousands of years in many east Asian countries, and the key ingredient, patchouli alcohol (PA), has been observed to exert anti-H. pylori and anti-urease activities. PurposeWe investigated the effect of PA on H. pylori urease and its subsequent influence on macrophage phagosome maturation and function. MethodsIn H. pylori experiment, the berthelot method and pH shock assay were adopted to evaluate the effect of PA on extracellular and intracellular H. pylori urease. And then, Q-PCR and Western blot were carried out to analyze the alterations in the expression of urease-related genes and proteins after PA treatment. In the H. pylori and macrophage cell (RAW264.7) co-culture experiment, the effects of PA on H. pylori-induced phagocytosis and intracellular killing of RAW264.7 were investigated using gentamycin protection assay, and the underlying mechanism was explored by immunofluorescence. ResultsPA at 25 and 50 μM inhibited intracellular H. pylori urease activity but not isolated urease by down-regulating the gene expression levels of ureB, ureE, ureI and nixA and reducing the protein expression level of UreB, thereby inhibiting the acid resistance of H. pylori. PA also recovered the function of macrophage bacterial digestion, and prior treatment with ammonium chloride inhibited the efficacy of PA. ConclusionPA suppressed intracellular H. pylori urease function and maturation, which increased macrophage digestion ability.

Synthesis, Antioxidant and Antiurease Activities of Some New 5,6- dichloro-2-(4-fluorobenzyl)-1H-benzimidazole Derivatives Containing Furan, Oxadiazole, Triazole and Thiadiazole Moieties

Background:Benzimidazoles and its derivatives have been attracting interest for many years because of their biological activities. Benzimidazoles containing different heterocyclic moieties have wide range of biological activities such as antimicrobial, antioxidant, anticancer, antiviral, etc.Methods:In this study, some benzimidazole derivatives containing furan, oxadiazole, triazole and thiadiazole moieties have been synthesized and then evaluated for their antioxidant and antiurease activities.Results:The results showed that all the tested benzimidazoles indicated remarkable urease inhibitory potentials with IC50 values ranging between 0.303±0.03 to 0.591±0.08 µM.Conclusion:In conclusion, synthesized benzimidazole derivatives showed good antioxidant and antiurease activities. Heterocyclic groups on benzimidazole nucleus enhance the activities.

Antimicrobial, antioxidant, anti-tyrosinase and anti-urease activities and FT-IR analyses of Helichrysum graveolens (Bieb) Sweet

Helichrysum graveolens (Bieb) Sweet possesses various medicinal applications such as diuretic, treatment of the sand and stone in kidney, regulation of digestion problems and strenghtening of the immune system. The investigation was carried out to reveal ethanol extracts of flower and stem parts of H. graveolens for antimicrobial, antioxidant, anti-tyrosinase and anti-urease activities. Ethanol extract of stem part of H. graveolens exhibited more antibacterial activity against growth of bacteria except for K. pneumoniae. Stem part of H. graveolens has higher copper reducing antioxidant capacity (CUPRAC) and anti-urease activities than flower part of H. graveolens. Anti-tyrosinase activity (IC50 values) of stem and flower parts of H. graveolens was found to be 0.01549 ± 0.0006 μg/ml and 0.01515 ± 0.0016 μg/ml, respectively. This survey suggests that ethanol extracts of different parts of H. graveolens is an alternative source for natural antioxidant and antimicrobial compounds, urease and tyrosinase inhibitors that could be utilized in drug and food industries.

The Investigation of Anti-Urease and Anti-Elastase Activities of Firstly Synthesized Eperezolide-like Derivatives

İlk defa sentezlenmiş olan oksazolidinon türevi eperezolid benzeri bileşiklerin antiüreaz ve anti-elastaz aktiviteleri incelendi. En yüksek ve en düşük antiüreaz aktivite sırasıyla 8 (IC50 = 1.91x10-3 ± 2.97x10-4 μM) ve 10 bileşiklerinde (IC50 = 6,03x10-3±1,98x10-4 μM) gözlendi. En yüksek ve en düşük anti-elastaz aktivite ise sırasıyla 8 (IC50 = 2,2x10-2 ± 2,6x10-3 μM) ve 1 bileşiklerinde (IC50 = 4,1x10-2 ±1,3x10-3 μM) gözlendi.

Phenolic profile of three wild edible mushroom extracts from Ordu, Turkey and their antioxidant properties, enzyme inhibitory activities

PurposeMushrooms have always been treasured and appreciated, thanks to their nutritional as well as medicinal properties. The purpose of this paper is to reveal these properties such as antioxidant activities and enzyme inhibition potentials of three mushroom species from Ordu, Turkey. Furthermore, phenolic profiles which are believed to be source of these properties are investigated.Design/methodology/approachThe assays followed to determine total phenolic, flavonoid and antioxidant contents, antioxidative and enzyme inhibition activities are spectrophotometric methods. Phenolic profiles of mushroom samples were investigated by using the HPLC system.FindingsThe highest phenolic content was found for Lactarius deliciosus. Pyrogallol was the major phenolics in all three samples. Total phenolic content values supported that finding. But, total flavonoid content was the maximum for Cantharellus cibarius. The magnitude of the antioxidant activities revealed by the different tests varied between species. Furthermore, inhibition potential degrees on acetylcholinesterase, butrylcholinesterase, tyrosinase and urease activities were worth mentioning. Lactarius pyrogalus had anti-tyrosinase activity with a 26.229 percent inhibition rate. IC50 values for urease inhibition effect of mushroom samples were in the range of 0.37–0.90 mg/mL.Originality/valueEnzyme inhibitory potentials for L. pyrogalus was revealed first time. On the other hand, studies on anti-tyrosinase activity of mushrooms are very rare, while almost no studies have been conducted on anti-urease activity. So, the results of present study are very valuable. Thus, the obtained data not only increase the ecological importance of the region but also provide significant contributions to the literature in terms of new sources rich in antioxidants.

Qualitative and quantitative phytochemical analysis and in-vitro biological activity of Rheum ribes L. different parts

The methanol extracts from different parts of Rheum ribes were subjected to qualitative and quantitative phytochemical and in vitro biological activity (antioxidant, anti-urease, anticholinesterase). Qualitative phytochemical tests were performed using standard analysis methods and these studies revealed the presence of phenolics and tannins. Following this, a quantitative determination of total phenolics and tannins contents was carried out. The antioxidant activity of the extracts were assayed using DPPH, FRAP, TEAC/ABTS and CUPRAC techniques. In addition, the anti-urease and anticholinesterase activity of the extracts were examined using indophenol and Ellman methods, respectively. In this study, it was determined that the macerated flowers extract contained higher total phenolic and tannins contents than the other extracts. According to the results obtained from the antioxidant experiment, the macerated extract of flowers showed the strongest ABTS.+ scavenging and ferric reducing antioxidant power activity. The macerated leaves and Soxhlet radix extracts exhibited the strongest DPPH. scavenging and cupric reducing antioxidant activity, respectively. The young shoots extracts obtained using the Soxhlet methods showed the highest anticholinesterase activity. All extracts obtained from different parts of the plant were found to have very low anti-urease activity when compared to the anti-urease activity of standard compound. Therefore, methanol extracts from plant’s flowers, leaves and young shoots can be used as a natural antioxidant and anticholinesterase agent respectively, for the pharmaceutical and food industry in the future.

Synthesis, antimicrobial, antioxidant, cytotoxic, antiurease and molecular docking studies of N-(3-trifluoromethyl)benzoyl-N′-aryl thiourea derivatives

An irrefutable advancement has been noted for the infectious diseases caused due to ureolytic bacteria through the development of various drugs. Keeping in mind the extremely valuable synthetic utility and medicinal significance of thiourea derivatives, synthesis of new 3-trifluoromethyl benzoic acid thiourea derivatives (3a–j) were carried out. The biological potential of all compounds in terms of antimicrobial, antioxidant, cytotoxic and antiurease activities were studied. The compounds 3a, 3c and 3i with dichloro and methoxy groups substitution on the aryl group showed significant activity against all strain of bacteria while moderate to no activity was observed in remaining compounds. Whereas the antifungal evaluation showed that all compounds were active againts C. Albican and no activity was observed against C. Prapsilosis. The cytotoxic findings revealed the non-toxic nature of these compounds as IC50 values of majority of the compounds are above 100 μm except for compounds 3f and 3g. In addition, these compounds exhibited better antioxidant potential as 100 μm concentration inhibited >50% reactive oxygen species (ROS) production except compounds 3e, 3f and 3j. The compound 3a proved to be the most potent urease inhibitor showing the highest enzyme % inhibition (93.1%) with IC50 value of 8.17 ± 0.24 µM and found more active as compare to standard followed by compound 3e (92.6%), 3h (91.6%), 3d (90.8%), 3b (90.6%) and 3f (90.0%) with their respective IC50 values. All the synthesized compounds were docked into the binding cavity of Urease (PDB ID: 4ubp). The most active compound 3a was also ranked as top on the docking score as it was found to show valuable interactions with the target protein along with good docking scores. Hence our results revealed that the synthesized compounds have potential to be used as potent urease inhibitors after further detailed mechanistic studies.

Synthesis of novel Schiff bases and azol-β-lactam derivatives starting from morpholine and thiomorpholine and investigation of their antitubercular, antiurease activity, acethylcolinesterase inhibition effect and antioxidant capacity

In this study, new Schiff bases and β-lactam derivatives containing morpholine and thio morpholine nuclei were synthesized. Antimicrobial, antioxidant, antimicrobial and antioxidant properties of all synthesized compounds were investigated and highly effective products were obtained. In this context, new effective structures were introduced to the literature.

Synthesis of novel Azol-β-lactam derivatives starting from phenyl piperazine and investigation of their antiurease activity and antioxidant capacity comparing with their molecular docking studies

This study reports the synthesis, biological investigation and molecular docking of novel β-lactam derivatives bearing 1,3,4-thiadiazole and 1,3,4-oxadiazole ring system. The synthesized compounds were evaluated for in vitro antiurease activity and antioxidant capacity. Almost all compounds showed excellent antiurease activity compared to thiourea, standard drug. Also, in silico ADME (absorption, distribution, metabolism, elimination) prediction and molecular docking studies were performed.

Phenolic Profile and Cholinesterase, Tyrosinase, Urease and Lipid Peroxidation Inhibition Potentials of Artemisia argyi from Ordu, Turkey

The present study was designed to reveal a natural resource that could cure for today’s major diseases such as Alzheimer, Parkinson and bacterial infection. Furthermore, oxidative stress resulting from lipid peroxidation is a precursor for many diseases. Therefore, anticholinesterase, antityrosinase, antiurease activities and the inhibition potential on lipid peroxidation of methanolic extract of Artemisia argyi collected from Ordu region were tested. The inhibition ratio of extract at 0.3 mg/mL concentration for asetylcholinesterase and butrylcholinesterase were calculated as 8.45 and 10.68%, respectively. IC50 values for tyrosinase and urease inhibition properties were also found as 0.505 mg/mL and 0.225 mg/mL. The all obtained values were compared with known corresponding inhibitors such as galantamine, kojic acid and thiourea. Besides these, 0.1 mg/mL of the extract prevented lipid peroxidation in the ratio of 7.19%. In the scope of this study, the phenolics of the leaves of A. argyi were also analyzed by using HPLC system and pyrogallol was identified as the major component with the 30.16 mg/kg concentration. On the other hand, benzoic acid was not detected in extract. According to obtained results, A. argyi from Ordu, has the proposed characteristics that it can be a natural resource that can be used in the field of medicine for treatment of various diseases especially Alzheimer and Parkinson, in the cosmetic industry for the elimination of skin problems and in the agricultural field in order to prevent the loss of nitrogenous components.