Anti-urease Activity Research Articles

Synthesis of newly designed hydrazones, in vitro and in silico studies, and structure-activity relationship

Herein, new N'-(substituted benzylidene)-3,5-dihydroxybenzohydrazide (1–13) series were synthesized, and their antioxidant, anticholinesterase, anti-tyrosinase, anti-urease, and antidiabetic activities were investigated together with in silico studies. The synthesized derivates were characterized using molecular spectroscopy, and the structure-activity relationships (SAR) were discussed for all tested biological assays. According to activity results, compound 3 exhibited excellent antioxidant activity in all tests, while compound 1 demonstrated the best acetylcholinesterase (AChE) inhibitory and butyrylcholinesterase (BChE) inhibitory activities. On the other hand, compound 11 showed excellent tyrosinase inhibitory (IC50:3.02±0.10 mM) and urease inhibitory (IC50:9.21±0.27 µM) activity. Moreover, among the synthesized compounds, compound 6 was detected as the best antidiabetic compound by inhibiting α-amylase (IC50:30.68±0.94 µM) and α-glycosidase (IC50:41.35±0.03 µM) enzymes, which were related with the antidiabetic activity. Molecular docking analysis confirmed AChE, BChE, tyrosinase, urease, α-amylase, and α-glucosidase inhibitory activities. In line with the findings obtained from in vitro bioactivity results and molecular docking analysis, hydrazone compounds are a suitable class of organic compounds for developing acetylcholinesterase, butyrylcholinesterase, urease, α-amylase, and α-glucosidase inhibitors.

Antioxidant and anti-urease activities of Cardamine bulbifera: Insights from molecular docking and density functional theory studies

IntroductionCardamine bulbifera (L.) Crantz, commonly known as “Asian bittercress”, is a plant species widely distributed across Asia. It belongs to the Brassicaceae and has been traditionally used in medicinal applications. This study investigates the phytochemical composition, phenolic content, antioxidant properties, and anti-urease activity of C. bulbifera. MethodsIn this study, the aerial parts of the C. bulbifera were collected. The total polyphenol content of the extracts was determined using spectrophotometric methods, and its antioxidant and anti-urease activities were assessed. The chemical composition was characterised using gas chromatography-mass spectroscopic (GC-MS) analysis. Additionally, molecular docking studies explored potential interactions between the identified compounds and Helicobacter pylori CagA oncoprotein. Furthermore, Density Functional Theory (DFT) analysis provided valuable insights into the electronic properties of the main compounds. ResultThe total phenolic content of C. bulbifera extract was 225 ± 0.02 mg GAE/g extract DW, and the total flavonoid content was 62.64 ± 3.27 mg QE/g extract DW. The 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assay revealed an IC50 value of 1.01 ± 0.04 mg/mL, indicating significant antioxidant activity. The IC50 value for anti-urease activity was determined to be 2.74 ± 0.03 µg/mL, suggesting potent inhibition of urease enzyme activity. GC-MS analysis identified 15 bioactive compounds in the extract. Molecular docking studies highlighted Phenol, 3,5-bis(1,1-dimethylethyl) and 1-dodecanol as compounds with the highest binding affinity for the H. pylori CagA oncoprotein, suggesting potential therapeutic implications against H. pylori-related cancers. Additionally, DFT analysis emphasised these compounds' electronic properties and chemical reactivities, indicating their potential role in future pharmaceutical developments. ConclusionC. bulbifera exhibits rich phenolic and flavonoid content and significant antioxidant and intense urease inhibition activities. These findings suggest that C. bulbifera may offer potential therapeutic options for conditions related to H. pylori infections, including cancer. Further research is needed to explore its mechanisms of action and clinical applications in more detail.

Jack bean urease inhibition by different root fractions of Cleome gynandra L – Kinetic mechanism and computational molecular modelling

Natural products with urease inhibiting potentialities would be valuable for enhancing nitrogen fertilizer formulations and developing new therapeutics against infectious diseases. Main focus of this research was to assess the inhibitory impact of various parts of Cleome gynandra (Cleomaceae) on jack bean urease activity, identify the responsible compounds, and ascertain their mode of enzyme inhibition and interactions with urease enzyme. Urease inhibitory potentiality of different plant parts of C. gynandra was determined using the phenol-hypochlorite method and mode of enzyme inhibition by Lineweaver-Burk kinetic analysis. LC-HRMS was carried out to identify the compounds of the active fractions. Molecular docking and simulations were executed to find out the binding affinity and interaction pattern of the isolated compounds at the active site of urease enzyme and to verify stability of protein-inhibitor complexes. The root of C. gynandra exhibited highest urease inhibitory potentiality with IC50 value of 1.529 mg/ml compared with leaf and stem. Among the different root fractions, water fraction revealed maximum anti-urease activity with IC50 values of 1.477 mg/ml followed by methanol (1.655 mg/ml) and acetone fractions (1.955 mg/ml). Inhibition kinetics indicated that these fractions were strong inhibitors of urease and exhibited a non-competitive mode of inhibition with Ki values of 184.911 µg/ml, 147.34 µg/ml, and 233.75 µg/ml respectively at 1000 mg/L concentration. LC-HRMS analysis confirmed the occurrence of glucocapparin, fluticasone propionate and lauryl hydrogen sulfate etc. in water fraction. Molecular modelling and simulation study suggested strong and stable interactions between the specified compounds of water fraction and active site of urease. Hence, the water fraction of C. gynandra roots represent a valuable source of natural urease inhibitors, for possible therapeutic applications and sustainable agricultural practices.

Novel Copper (II) Complexes with Fluorine-Containing Reduced Schiff Base Ligands Showing Marked Cytotoxicity in the HepG2 Cancer Cell Line.

Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring-the dichloro[(±)-trans-N,N'-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC50 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC50 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC50 values in the lower micromolar region.

Exploring the Bioactivity of Siddhalepa Asamodagam Spirit from Seeds of Trachyspermum roxburghianum (DC.) H. Wolff

Objectives The water distillate derived from Trachyspermum roxburghianum seeds has been traditionally employed in medicine for treating stomach infections and gastric ulcers. However, no systematic study has been conducted to evaluate its efficacy. Therefore, the present study focused on evaluating the potential health benefits, including the chemical constituents of the distillate. This distillate was prepared and identified as Siddhalepa Asamodagam Spirit (Sid.AS). Methods The chemical constituents of Sid.AS were identified and quantified using Gas Chromatography-Mass Spectrometry (GC-MS) method. The antioxidant potential of Sid.AS samples was assessed in vitro using DPPH and ABTS assays. Various concentrations of Sid.AS were subjected to antimicrobial, anti-obesity, anti-diabetic, anti-inflammatory, and urease inhibition assays according to the standard methods specified by the Ayurvedic Department in Sri Lanka. Results Thymol was identified as the major compound in Sid.AS through GC-MS analysis. Sid.AS demonstrated significant anti-urease, anti-inflammatory, anti-lipase, and antioxidant activities, as evidenced by low IC50 values compared to the positive controls. This suggests its potential in controlling gastric-related disorders, scavenging free radicals, and managing obesity by inhibiting the breakdown and absorption of fats. Additionally, Sid.AS exhibited inhibitory effects against alpha-amylase and alpha-glucosidase enzymes, indicating potential anti-diabetic activity by regulating blood sugar levels. Sid.AS displayed strong antimicrobial activity against tested microorganisms, with higher zones of inhibition and lower MIC and MLC values, indicating its effectiveness in combating microbial infections. Findings from the anti-lipase assay demonstrated activity comparable to that of the positive control, Orlistat. Conclusion The findings of Sid.AS suggest its potential as a multi-functional bioactive herbal distillate with various pharmacological activities. Our results highlight that Sid.AS is a promising natural herbal extract with diverse pharmacological properties, including anti-urease, antioxidant, anti-inflammatory, anti-diabetic, anti-obesity, and antimicrobial activities. Further research and development could explore its potential applications in various therapeutic areas.

A REVIEW ON CURRENT TRENDS IN Helicobacter pylori MANAGEMENT WITH MEDICINAL PLANTS AND ITS CONSTITUENTS

Helicobacter pylori is a bacterium associated with gastric diseases and disorders of the upper gastrointestinal tract. The gram-negative bacterium Helicobacter pylori is known as a persistent colonizer of the human stomach, and this bacteria is also involved in extra-intestinal diseases. In 1994, the International Agency for Research on Cancer, World Health Organization classified H. pylori as a class 1 carcinogen, the only bacterium given this classification. Besides, the emergence of H. pylori resistance to antibiotics has been a major clinical challenge in the field of gastroenterology, and this concern has been shown an increasing tendency in many regions of the world. To overcome the current circulating difficulties, new potential therapeutic targets were uncovered to find active substances for the treatment of H. pylori infection. Several medicinal plants and their isolated compounds have been reported for their antimicrobial activity against H. pylori. It is demonstrated that they are efficacious against H. pylori strains that are resistant to drugs. The mechanism of action of many of these plant extracts and plant-derived compounds is different from that of conventional antibiotics. Therefore, natural compounds are emerging as a potential source of raw materials with diverse mechanisms of action. Some commonly known mechanisms can be listed as anti-urease activity, anti-adhesive activity, anti-inflammatory and gastroprotective activity, and effects on the oxidative stress process. Recently, new classes of drugs with reasonable antibacterial mechanisms against H. pylori have also been mentioned, including (1) anti-biofilm agents, (2) anti-virulence molecules (anti-VacA, anti-CagA agents, toxin BabA and LPS inhibitors, anti-motility agents, Helicobacter pylori quorum sensing inhibitors), (3) mucolytic agents, and (4) compounds that impact on essential proteins in the physiology of H. pylori such as inosin-5‘monophosphate dehydrogenase and HsrA inhibitors. This review article aims to summarize current prospects, identify possible novel targets, and be considered as a complementary therapy in the eradication treatment against Helicobacter pylori.

Fluoroquinolone and enoxacin molecules are potential urease inhibitors for treating ureolytic bacterial infections

Urease, a nickel-dependent metalloenzyme, has emerged as a significant therapeutic target due to its role in promoting the pathogenesis of various human health conditions. These include the development of pyelonephritis, urolithiasis, peptic ulcers, hepatic encephalopathy, and gastric ulcers. The currently available treatment involved the usage of strong antibiotics along with proton pump inhibitors to cope with the infection of urease producing bacteria. These conventional treatments are becoming less effective as bacteria are gaining multiple drug resistance. Therefore, there is a crucial need to identify alternative compounds with potential anti-urease activity and minimal side effects. Fluoroquinolones and Enoxacin derivatives offer antimicrobial, anti-inflammatory, antioxidant, anti-diabetic, and anti-urease activities. To improve the chemical diversity of urease inhibitors, different series of fluoroquinolones and Enoxacin derivatives were evaluated against urease and their antioxidant activity was also evaluated. To achieve this objective, in-silico studies were conducted utilizing molecular docking and adsorption, distribution, metabolism, excretion, and toxicology (ADMET) models. These analyses were employed to explore potential binding mechanisms and assess the drug-likeness of the compounds against urease enzymes. The inhibitory effect of docked heterocyclic compounds was also verified in-vitro against urease enzyme. Fluoroquinolones derivatives were found to be active inhibitors at high dose levels but showed minimum inhibition at low concentration. The compound EN from the Enoxacin series exhibited the highest potency as a urease inhibitor, with an IC50 of 45.86 μM, out-performing the standard drug thiourea, which had an IC50 of 52.20 μM. Additionally, compounds NOX-3 and FB-17 from the fluoroquinolone and Enoxacin series demonstrated significant DPPH free radical scavenging activity, with IC50 values of 98.17 μM and 97.98 μM, respectively. These results were comparable to the positive control ascorbic acid, which had an IC50 of 48.15 μM. This study demonstrates that Enoxacin derivatives can be further analyzed as potent urease inhibitors, while both Enoxacin and fluoroquinolone derivatives can be developed into more effective drugs to overcome oxidative stress.

Recent Advances in Anti-Urease Activity of Schiff Bases and their Metal Complexes

The urease enzyme, found in plants, fungi and bacteria, plays a crucial role in catalyzing the hydrolysis of urea, a process integral to microbial metabolism. Its ureolytic activities have garnered significant attention for their impact on agriculture and the health of living organisms. Notably, urease activity in the human stomach, urinary tract and animal cells can lead to pathogenic outcomes. Schiff bases, characterized by their carbonyl-type imine or azomethine linkage, are recognized for their diverse biological effects, including anti-urease activity. Additionally, the metal complexes derived from the Schiff bases demonstrate controlled urease inhibition activity, influenced by factors such as the type of metal, its oxidation state and the coordination environment. This inhibition occurs through the interaction of the Schiff base ligand with the nickel containing active site of urease or the protein sphere surrounding the metal, disrupting the ureolytic mechanism. In this review, the utilization of Schiff bases and their metal complexes in urease inhibition is highlighted as explored by various research groups.

Correlation between in vitro anti-urease activity and in silico molecular modeling approach of novel imidazopyridine–oxadiazole hybrids derivatives

Abstract In the current era, a potent drug is still needed on the market for the treatment of various diseases worldwide. Researchers mainly focus on those enzymes that cause these diseases. One of the major diseases is caused by an enzyme called urease, which increases the concentration of ammonia in the body upon hydrolysis. Researchers across the globe have keen interest to synthesize the potent inhibitor for this conversion. From this perspective, hybrid analogs of imidazopyridine and oxadiazole (1–20) were designed and efficiently synthesized followed by characterizing them through varied spectroscopic methods (1HNMR, 13CNMR, and HREI-MS). In addition, in vitro analyses of the synthesized compounds were conducted to evaluate their anti-urease potency. There was significant potential in most compounds analyzed, but analogs 15, 16, and 17 (IC50 = 2.20 ± 0.10 μM, IC50 = 2.50 ± 0.10 μM, and IC50 = 2.30 ± 2.10 μM, respectively) performed exceptionally well in comparison with thiourea (IC50 = 22.30 ± 0.44 μM). The selected candidates were further investigated under a molecular docking study to confirm protein ligand interactions. In addition, energy gap (E gap) of the HOMO–LUMO was explored via density functional theory studies.

Chemical Composition and In Vitro Biological Activity of Two Thymus L. Varieties Growing in Turkey

Thymus kotschyanus var. kotschyanus (TKK) and T. kotschyanus var. glabrescens (TKG) varieties were used as both spice and medicine by the people in Turkey. It was determined that plants’ methanol extracts had the strongest antioxidant, anticholinesterase, antiurease activity and high total phenolic contents. The ethyl acetate and methanol extracts were found to have strong antimicrobial activity. Methanol extracts showed low hemolytic effect against human erythrocytes. It was determined that TKG extract showed higher anti-proliferative effect compared to TKK extract. Both plants extract significantly decreased reactive oxygen species (ROS) generation in cancer cells. It was determined that amounts of chlorogenic and rosmarinic acid compounds were similar in both plants, but apigenin 7-O-neohesperidoside compound was found in higher amounts in TKK. The findings obtained in this study suggest that methanol and ethyl acetate extracts obtained from these two species can be used as antioxidant, anticholinesterase, antimicrobial and antiurease agents. The findings support the traditional use of these species.

Antiurease Activity of Antibiotics: In Vitro, In Silico, Structure Activity Relationship, and MD Simulations of Cephalosporins and Fluoroquinolones.

Helicobacter pylori infection is widespread in 50% of the world's population and is associated with gastric ulcers and related disorders that ultimately culminate in gastric cancer. Levofloxacin-based, or clarithromycin-based, triple therapy is frequently used to inhibit the bacterial urease enzyme for the eradication of H. pylori. A comprehensive investigation based on the urease inhibitory profiles of antibiotics and their computational implications is lacking in the scientific literature. The present study was aimed specifically to determine the antiurease activities within the realms of cephalosporins and fluoroquinolones by in vitro methods supported with in silico investigations. The results demonstrate the jack bean urease inhibitory activity of cephalosporins, wherein cefadroxil, cefpodoxime, cefotaxime, and cefaclor displayed inhibitions (IC50 21.35 ± 0.64 to 62.86 ± 0.78 μM) compared with the standard thiourea (IC50 21.25 ± 0.15 μM). Among fluoroquinolones, levofloxacin, ofloxacin, and gemifloxacin (IC50 7.24 ± 0.29 to 16.53 ± 0.85 μM) unveiled remarkable inhibitory profiles. Levofloxacin and ofloxacin exhibited competitive inhibition against the said enzyme. Ciprofloxacin and moxifloxacin displayed weak urease inhibitions. During molecular docking studies, Asp362, Gly279, Arg338, Asn168, Asp223, Gln364, and Met366 were involved in hydrogen bonding in fluoroquinolones, and hydrogen bonding was established with Arg338, His248, Asn168 residues, and metal Ni601 and Ni602 of the enzyme. MD simulations and MMPBSA results demonstrated the existence of significant protein-ligand binding. Overall, these results warrant further investigations into the significance of these active molecules in relation to their inhibitory potential against the targeted urease enzyme.

In vitro anti-Helicobacter pylori, anti-urease and anti-gastric cancer activities of novel hydrazones

In this study, new hydrazone derivatives were synthesized by taking into account the virulence factor of the urease in the urease-positive microorganism H. pylori. The structure of synthesized compounds 3a-3j was confirmed using 1H NMR, 13C NMR and elemental analyses. After structure confirmations all compounds were evaluated for in vitro urease inhibitory and anti-H. pylori activities. Furthermore, since H. pylori infection is associated with gastric cancer, the effects of the synthesized compounds against two different gastric cancer cell lines (SNU1 and AGS) were also evaluated. Amongst the series, two compounds 3c and 3j were found to be excellent inhibitors of urease, having IC50 values of 9.813 ± 0.403 µM and 11.407 ± 0.393 µM, better than the standard thiourea (IC50 = 13.428 ± 0.587 µM), whereas the remaining compounds displayed moderate activity. Compounds 3c and 3d were found to be the most active in the series against H. pylori with MIC values 4 µg/mL and 5 µg/mL. Next, compounds were evaluated as anti-gastric cancer activity and the compounds 3c and 3j were more potent than reference drug cisplatin against SNU1 and AGS. The docking study was executed to analyzed the interaction between the active site of the urease and the compounds 3c and 3j. When the all activities (anti-H. pylori, anti-urease and anti-gastric cancer activities) examined, it was found that the presence of the nitro group, which is an electron withdrawing group, in the 5th position of the thiophene ring (compound 3c) increased all activities. From the structure-activity relationship, it has been observed that the compound 3c showed excellent potential for anti-H. pylori, anti-gastric cancer and can be alternative therapy in the future.

Molecular Docking and DFT Analysis of Thiazolidinone-Bis Schiff Base for anti-Cancer and anti-Urease Activity

This reearch focused on the structural characterization of (2Z,5E)-2-(((E)-benziliden) hidraziniliden)-5-(nitro(fenil)metilen)-3-feniltiazolidin-4-on molecule (Thiazolidinone-Bis Schiff Base). Depending on the molecule's stability phase geometry, all analyses have been carried out utilizing the B3PW91 technique with 6-311++G(d,p) and SDD basis sets, for structural characterisation. Many computations were performed in our work, including inter-orbital and inter-orbital bond interactions, HOMO-LUMO energy deficiencies, and electrostatic surface mapping processes of the Thiazolidinone-Bis Schiff Base. In a subsequent investigation, we have used molecular docking to analyze the particular binding place and method of the ligand onto the protein. Schiff Thiazolidinone Molecular docking results against cancer and urease enzymes were obtained.

Synthesis of Carbothioamide Substituted Benzimidazole Compounds and Investigation of Biological Activities

Yapılarında bir oksijen atomu ile birlikte nitrojen içeren heterosiklik bileşikler, çeşitli biyolojik uygulamaları nedeniyle önemli bir tıbbi kimya bileşikleri sınıfıdır. Benzimidazoller de bu grupta yer alıp, halka yapısında farklı yapıda iki azot (N) atomu taşıyan heterosiklik bir aromatik organik bileşiktir. Yapılan bu çalışmada, sentezlenen benzimidazol türevlerinin (1-5) antiüreaz ve antioksidan aktiviteleri spektrofotometrik metotlarla incelendi. Antioksidan aktivitesinin kanıtı bizlere vücutta oluşabilecek hastalıklara karşı savunma mekanizmasının var olduğunu açıkça göstermektedir. Sentezlenen tüm benzimidazol bileşikleri antiüreaz ve antioksidan aktivite gösterdi. Üreaz inhibisyon aktivitesi gösteren en güçlü bileşik 2 numaralı, en az aktif bileşik ise 4 numaralı bileşiktir. Tüm bileşikler tiyoüreden daha yüksek aktivite gösterdi. En yüksek antioksidan aktivitesine sahip bileşik 5 numaralı bileşik, en düşük antioksidan aktivitesine sahip bileşik ise 4 numaralı bileşikler olarak belirlendi.

Antimicrobial, Antibiofilm and Antiurease Activities of Microbially Synthesized Silver Nanoparticles against Proteus mirabilis

Nanoparticles (NPs) are tiny materials ranging in size from 1 to 100 nm and have unique magnetic, electrical, and optical characteristics differing from bulk materials. They have a broad spectrum of applications in different industries. Several physical and chemical techniques have been applied to produce metal NPs. Alternatively, green synthesis offers an environmentally friendly and simple means for NP preparation. In the present study, silver NPs were produced by the Pseudomonas aeruginosa OG1 strain. Characterization of NPs was performed by TEM, SEM, and XRD. These NPs were used against pathogenic Proteus mirabilis, which shows high-level urease activity and forms clear biofilms. Silver NPs obtained in the present study were applied to inhibit the growth, urease production, and biofilm formation of P. mirabilis. Growth inhibition zones of 9 mm and 11 mm and, 60 % and 85% antibiofilm effects were obtained by 100 µg mL-1 and 200 µg mL-1 NPs, respectively. The urease activity of P. mirabilis was completely inhibited in both concentrations. These results show that AgNPs can be used as effective antimicrobial, antibiofilm, and antiurease agents in the fight against pathogens.

Citrus Honeys from Three Different Regions of Turkey: HPLC-DAD Profiling and in Vitro Enzyme Inhibition, Antioxidant, Anti-Inflammatory and Antimicrobial Properties with Chemometric Study.

The objectives of the present study are to compare the phenolic profiles and biological activities of 15 citrus honey samples from three different locations in Turkey using a chemometric approach. The HPLC-DAD analysis was used to determine phenolic profiles. Nineteen phenolic compounds were identified. Gallic acid (107.14-717.04 μg/g) was recorded as the predominant compound. AF (Antalya-Finike) had the highest antioxidant activity in ABTS⋅+ (IC50 : 18.01±0.69 mg/mL), metal chelating (IC50 : 6.20±0.19 mg/mL) and CUPRAC (A0.50 : 12.05±0.68 mg/mL) assays, while it revealed the best anti-inflammatory activity against COX-2 (17.28±0.22 %) and COX-1 (43.28±0.91 %). AM (Antalya-Manavgat) was the most active in β-carotene-linoleic acid (IC50 : 10.05±0.19 mg/mL), anti-urease (38.90±0.69 %), anti-quorum sensing and antimicrobial activities. AKO1 (Adana-Kozan-1) in DPPH⋅ (IC50 : 34.25±0.81 mg/mL) assay, AKU1 (Antalya-Kumluca-1) in tyrosinase inhibition activity (37.73±0.38 %) assay, AKU2 (Antalya-Kumluca-2) in AChE (10.55±0.63 %) and BChE (9.18±0.45 %) inhibition activity assays showed the best activity. Chemometric tools were applied to the phenolic compositions and biological properties. PCA and HCA ensured that 15 citrus honey samples were grouped into 3 clusters. The results showed that myricetin, kaempferol, vanillin, protocatechuic acid, rosmarinic acid, rutin, vanillic acid, gallic acid, catechin and p-hydroxyphenyl acetic acid are phenolic compounds that can be used in the classification of citrus honeys.

A Study on Recognizing the Value of Chestnut (Castanea sativa) Blossom Waste

Chestnut (Castanea sativa) blossoms are natural resources that are not put to economic use and that are completely mixed as waste with the soil. To carry out the potential usefulness of chestnut blossoms, this extensive study was designed and it got out some remarkable results. In addition to the phenolic capacity and antioxidant capacity of the aqueous and ethanolic extracts of dried chestnut flowers, the anti-urease activity of these extracts was studied to demonstrate their therapeutic value. The binding interaction of the phenolic substances present in chestnut blossom with urease was shown using molecular docking research. The aqueous extract had total phenolic content of 45 mg GAE/g, and total flavonoid content of 6 mg QUE/g, also rutin was found as the dominant compound by HPLC. IC50 values of urease of the aqueous and ethanolic extracts were 2.55 mg/mL and 4.45 mg/mL, respectively. According to the docking experiments which were important for supporting the idea of anti-urease activity, myricetin and luteolin showed different and effective bounding degrees to the target protein when compared with the reference molecule acetohydroxamic acid. In summary, chestnut flowers are closely rich in phenolic compounds which are responsible for a wide range of biological activities such as antioxidants and urease inhibition, and these blossoms could be evaluated as important potential raw materials for the food.

Yeni Benzimidazol Bileşiklerinin Sentezi, Antioksidan ve Antiüreaz Aktiviteleri

Bu çalışmada, yeni bir seri benzimidazol türevi (1-5) sentezlenerek antioksidan ve antiüreaz aktiviteleri spektrofotometrik metotlarla incelendi. Sentezlenen yeni benzimidazol bileşiklerinin antioksidan aktiviteleri, DPPH (1,1-difenil-2-pikrilhidrazil) serbest radikal süpürme aktivitesi, ABTS (2,2'-azino-bis(3-etilbenzotiazolin-6-sülfonik asit) diamonyum tuzu) radikal süpürme aktivitesi, antiüreaz aktivite tayini ve demir indirgeme gücü gibi metodlarla tayin edildi. Antioksidanlar, reaktif oksijen çeşitlerinin meydana gelmesinin önlemek ve bunların oluşturmuş olduğu tahribatı engellemek için vücutta var olan bir tür savunma mekanizmalarıdır. Serbest radikalleri nötralize etmek amacıyla kullanılırlar. Antioksidan aktivitesinin kanıtı açıkça bizlere vücutta oluşabilecek hastalıklara karşı savunma mekanizmasının varlığını sergilemektedir. Elde edilen deneysel bulgulardan, benzimidazol bileşiklerinden özellikle 4 numaralı bileşiğin antioksidan aktivite değerlerinin diğer bileşiklere oranla daha yüksek olduğu saptandı. Tüm test bileşikleri, standart üreaz inhibitöründen (tiyoüre) daha yüksek aktivite gösterdi. En yüksek ve en düşük antiüreaz aktivite gösteren bileşikler sırasıyla 1 ve 5 numaralı bileşikler olarak belirlendi.

New Acetamide-Sulfonamide-Containing Scaffolds: Antiurease Activity Screening, Structure-Activity Relationship, Kinetics Mechanism, Molecular Docking, and MD Simulation Studies.

The development of novel scaffolds that can increase the effectiveness, safety, and convenience of medication therapy using drug conjugates is a promising strategy. As a result, drug conjugates are an active area of research and development in medicinal chemistry. This research demonstrates acetamide-sulfonamide scaffold preparation after conjugation of ibuprofen and flurbiprofen with sulfa drugs, and these scaffolds were then screened for urease inhibition. The newly designed conjugates were confirmed by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and elemental analysis. Ibuprofen conjugated with sulfathiazole, flurbiprofen conjugated with sulfadiazine, and sulfamethoxazole were found to be potent and demonstrated a competitive mode of urease inhibition, with IC50 (µM) values of 9.95 ± 0.14, 16.74 ± 0.23, and 13.39 ± 0.11, respectively, and urease inhibition of 90.6, 84.1, and 86.1% respectively. Ibuprofen conjugated with sulfanilamide, sulfamerazine, and sulfacetamide, whereas flurbiprofen conjugated with sulfamerazine, and sulfacetamide exhibited a mixed mode of urease inhibition. Moreover, through molecular docking experiments, the urease receptor-binding mechanisms of competitive inhibitors were anticipated, and stability analysis through MD simulations showed that these compounds made stable complexes with the respective targets and that no conformational changes occurred during the simulation. The findings demonstrate that conjugates of approved therapeutic molecules may result in the development of novel classes of pharmacological agents for the treatment of various pathological conditions involving the urease enzyme.

An overview ofthe privileged synthetic heterocycles as urease enzyme inhibitors: Structure-activity relationship.

Urease is a metalloenzyme including two Ni2+ ions, found in some plants, bacteria, fungi, microorganisms, invertebrate animals, and animal tissues. Urease acts as a significant virulence factor, mainly in catheter blockage and infective urolithiasis as well as in the pathogenesis of gastric infection. Therefore, studies on urease lead to novel synthetic inhibitors. In this review, the synthesis and antiurease activities of a collection of privileged synthetic heterocycles such as (thio)barbiturate, (thio)urea, dihydropyrimidine, and triazol derivatives were described and discussed according to structure-activity relationship findings in search of the best moieties and substituents that are answerable for encouraging the desired activity even more potent than the standard. It was found that linking substituted phenyl and benzyl rings to the heterocycles led to potent urease inhibitors.