Search

This study examines the chemical composition, antioxidant properties, and urease inhibitory effects of Hyoscyamus muticus L. subsp. falezlez (Coss.) Maire. Using LC-ESI-MS/MS, 19 distinct phenolic compounds were identified, with chlorogenic acid being the most abundant. The ethanol extract demonstrated notable antioxidant activity, highlighting its potential for therapeutic use. Urease inhibition assays revealed a remarkable 91.35% inhibition by the H. muticus extract, with an IC50 value of 5.6 ± 1.20 μg/mL, indicating its promising role in addressing conditions linked to urease activity. Molecular docking studies further investigated the interaction between H. muticus phenolic compounds and urease, identifying hyperoside as a leading candidate, with a binding energy of −7.9 kcal/mol. Other compounds, such as rutin, luteolin, apigenin, kaempferol, hesperetin, chlorogenic acid, and rosmarinic acid, also demonstrated significant binding affinities, suggesting their potential to disrupt urease function. These findings highlight the therapeutic potential of H. muticus as a source of natural bioactive compounds, offering promising avenues for the development of novel treatments for urease-related disorders and oxidative stress. [ABSTRACT FROM AUTHOR]

The phytochemical investigation of the aqueous methanolic extract of the aerial parts of Dioscorea preussii, led to the isolation of a new chalcone preussiate (1) along with 10 other compounds including xanthomicrol (2), cholestan-3-one (3), arjunolic acid (4), tormentic acid (5), ursolic acid (6), betulin (7), lupeol (8), p-hydroxybenzoic acid (9), isovanillin (10) and vanillic acid (11), being reported for the first time from this plant. Their structures were established by spectroscopic techniques including 2D NMR spectroscopy. All the isolates were subjected to the biological screening but only showed antioxidant and urease inhibitory properties. The compounds 1,8 and 11 displayed the most potent urease inhibitory properties with IC50 values, 22.4, 33.3 and 35.7 µM, respectively, while 3 was moderately active. The compound 11 showed potent antioxidant activity among all the tested isolates with an IC50 value of 45.3 µM. [ABSTRACT FROM AUTHOR]

Abstract Clinically significant problems such as kidney stones and stomach ulcers are linked to the activation of the urease enzyme. At low pH, this enzyme gives an ideal environment to Helicobacter pylori in the stomach which is the cause of gastric ulcers and peptic ulcers. In recent work, we have developed a library of 4-fluorocinnamaldehyde base thiosemicarbazones and assessed them for their potential against urease enzyme. The synthesized compounds displayed significant to moderate inhibition potential with IC50 values ranging from 2.7 ± 0.5 µM to 29.0 ± 0.5 µM. compound 3c displayed the highest inhibition potential followed by 3a and 3b. Two compounds of the series 3f and 3 g remained inactive against urease. The kinetic study of compound 3c exhibited a competitive type of inhibition with a K i value of 3.26 ± 0.0048 µM. SAR analysis was also thoroughly done. Molecular docking was used to analyze the interaction pattern of each derivative, and the outcomes demonstrated that the compounds had excellent binding interactions with the active site.

Designing and developing small organic molecules for use as urease inhibitors is challenging due to the need for ecosystem sustainability and the requirement to prevent health risks related to the human stomach and urinary tract. Moreover, imaging analysis is widely utilized for tracking infections in intracellular and in vivo systems, which requires drug molecules with emissive potential, specifically in the low-energy region. This study comprises the synthesis of a Schiff base ligand and its selected transition metals to evaluate their UV/fluorescence properties, inhibitory activity against urease, and molecular docking. Screening of the symmetrical cage-like ligand and its metal complexes with various eco-friendly transition metals revealed significant urease inhibition potential. The IC50 value of the ligand for urease inhibition was 21.80 ± 1.88 µM, comparable to that of thiourea. Notably, upon coordination with transition metals, the ligand–nickel and ligand–copper complexes exhibited even greater potency than the reference compound, with IC50 values of 11.8 ± 1.14 and 9.31 ± 1.31 µM, respectively. The ligand–cobalt complex exhibited an enzyme inhibitory potential comparable with thiourea, while the zinc and iron complexes demonstrated the least activity, which might be due to weaker interactions with the investigated protein. Meanwhile, all the metal complexes demonstrated a pronounced optical response, which could be utilized for fluorescence-guided targeted drug delivery applications in the future. Molecular docking analysis and IC50 values from in vitro urease inhibition screening showed a trend of increasing activity from compounds 7d to 7c to 7b. Enzyme kinetics studies using the Lineweaver–Burk plot indicated mixed-type inhibition against 7c and non-competitive inhibition against 7d. [ABSTRACT FROM AUTHOR]

Objective: The main objective of this work is to synthesize thiobarbituric acid based bis-Schiff base derivatives and to evaluate their ability to inhibit urease enzyme and DPPH free radical scavenging potential. Methods: Thiobarbituric acid derived bis-Schiff bases (IIIa–IIIi) were synthesized by treating 2,4-dihydroxybenzaldehyde and the starting moiety 1,3-diethyl-2-thiobarbituric acid in ethanol through refluxed followed by treating chloro ethyl acetate in DMF solvent. Subsequently, hydrazine hydrate was added to compound (II), yielding bis-hydrazide in better yield, which was further reacted via refluxed with benzaldehydes in ethanol, catalyzed by acetic acid to yield compounds (IIIa–IIIi) in excellent yields. Results: The resulting compounds were tested to inhibit urease enzyme and DPPH free radical scavenging activity. Among the series, compound (IIId) (IC50 = 16.11 ± 0.92 µM), (IIIc) (IC50 = 19.11 ± 0.55 µM), and (IIIf) (IC50 = 21.01 ± 1.42 µM) were found as promising lead urease inhibitors, stronger than the standard thiourea (IC50 = 21.15 ± 0.32 µM). Moreover, compound (IIIa) (IC50 = 40.21 ± 0.12 µM) was found as the excellent antioxidant agent comparing it with the standard ascorbic acid. Molecular docking study was performed to analyze the most potent compounds against urease enzyme. The results also shows that all compounds had good ADME properties there was no violation found in compounds ranges all are under druglikness criteria. Additional research combining in vivo, toxicological, and computational analyses can offer thorough understandings of the effectiveness, safety, and fundamental mechanisms of action of these potentially beneficial antioxidant substances. Conclusions: These compounds showed tremendous potential as DPPH free radical scavengers and urease enzyme inhibitors. Compound (IIId) demonstrated the greatest suppression of urease enzyme activity, however compound (IIIa) displayed superior antioxidant effects. Additional research, incorporating in vivo, toxicological, and computational examinations, is necessary to thoroughly assess the effectiveness, safety, and fundamental mechanisms of action of these intriguing antioxidant molecules. [ABSTRACT FROM AUTHOR]

Objective: To synthesize bis-Schiff bases bearing thiobarbituric acid and to screen their anti-urease inhibitory potential. Methods: In this study, 1,3-dimethylbarbituric acid derivatives were synthesized by a four-step process. Using K2CO3, 2,4-dihydroxy benzaldehyde and chloro ethyl acetate were esterified in DMF in the first step under reflux condition. The reaction was then carried out by combining the esterified aldehyde with 1,3-dimethylbarbituric acid at room temperature for about an 1 h. Hydrazine hydrate was then mixed with compound (II) in ethanol solvent with acetic acid acting as catalyst. Finally, substituted aromatic aldehydes were treated with bis-hydrazide (III) using ethanol and acetic acid as a catalyst. Results: The newly synthesized compounds were screened for their urease inhibition (in vitro). Four analogs, including (IIIj) (IC50 = 15.22 ± 0.49 μM), (IIIg) (IC50 = 16.05 ± 0.16 μM), (IIIa) (IC50 = 16.29 ± 0.73 μM), and (IIIb) (IC50 = 21.17 ± 0.21 μM) were found most powerful inhibitors than standard thiourea (IC50 = 22.80 ± 2.20 μM). The urease inhibition was also seen in compound (IIIi), (IIIc), (IIIh), (IIIe), (IIId), and (IIIf) however it was less from standard. The structure stability and chemical reactivity of the compounds were checked by density functional theory (DFT) method. Furthermore, the molecular docking simulation was performed to check the protein (urease) and ligand interactions and binding affinities by using AutoDock Vina. Conclusions: The synthesized derivatives attributed temendous potential against urease enzyme. Compound (IIIj) was found as the most potent anti-urease agent. Additional research including taxicological and in vivo is necessary to know the safety, effectivness and mechanism of action of these potent molecules. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A new series of azabenzimidazole compounds was synthesized and characterized with spectral methods such as IR, 1H NMR, 13C NMR and elemental analysis. The target compounds were screened for urease, and acetylcholinesterase inhibitory activities. The synthesized azabenzimidazole containing thiosemicarbazide and oxadiazole moieties showed antiurease activity. 2,2′-[(6-Bromo-2-oxo-1H-imidazo[4,5-b]pyridine-1,3-diyl)bis(1-oxoethane-2,1-diyl)]bis(N-4-nitrophenylhydrazinecarbothioamide) has the best inhibition result with IC50 = 15.80±0.40 µg/mL (15.75±0.15 µg/mL for thiourea). [ABSTRACT FROM AUTHOR]

The Asian region of earth has a rich agriculture system that provides extensive opportunities to boost pharmaceutical and nutritional research to address the use of food crops for health benefits and potential clinical applications. The traditionally cropped green leaf vegetable indigenously known as Bathu and botanically known as Chenopodium album (C. album) is traditionally used as a sedative, blood purifier, hepatoprotectant, diuretic, and antiscorbutic laxative. In this study, we investigated the anti-infection potential, anti-diabetic potential, and mineral composition of indigenously cultivated C. album plant extracts. Methanol and n-hexane solvents were used to extract phytochemicals at different extraction conditions. The maximum yield of 12.72 ± 0.36 g/100 g extract was obtained in methanol with 200 rpm shaking, 200 mL solvent, and an 8 h extraction period. Under the same conditions, n-hexane gave 2.09 ± 0.29 g/100 g extract. Good alpha-amylase inhibition efficiency was shown by the n-hexane extracts, while the methanol extracts showed good urease inhibition potential. The H6 extract had the lowest IC50 (8.16 ± 0.2 ug/mL) as compared to the standard acarbose (9.27 ± 0.6 ug/mL). Similarly, the M6 extract revealed a significant urease inhibitory potential, i.e., IC50 of 18.77 ± 0.6 ug/mL, which was close to the standard thiourea (IC50: 19.09 ± 0.7 ug/mL). Regarding the antibacterial study, the M6 extract showed 16.55 ± 0.57 mm ZOI against E. coli and 15.54 ± 0.55 mm in the case of S. aureus, as compared to the standard ciprofloxacin, which showed 26.08 ± 0.73 mm, and penicillin, which showed 21.12 ± 0.81 mm ZOI. Mineral profiling was investigated by ICP-OES, which showed significant amounts of Mg and Fe in all extracts. Our findings tend to show that systematic harvesting and utilization of this vegetable crop could be recommended as an alternative nutritional therapy in the management of internal infections and diabetes. [ABSTRACT FROM AUTHOR]

Three new trinuclear complexes containing either nickel(II), copper(II) or zinc(II), [Ni3L2(NO3)2(CH3OH)2]·2CH3OH (1), [Cu3Br2L2] (2), [Zn3L2(NCS)2(CH3OH)2]·0.5CH3OH·0.5H2O (3), and a new dioxidomolybdenum(VI) complex, [MoO2L] (4), have been prepared from the bis-Schiff base N,N'-bis(4-bromosalicylidene)-1,3-propanediamine (H2L) with various metal salts in methanol. The complexes were characterized by elemental analysis, IR and UV–Vis spectra. Molecular structures were confirmed by single crystal X-ray diffraction experiments. The Ni ions in 1 adopt an octahedral coordination environment, bridged by phenolate oxygen and nitrate ligands. The Cu ions in 2 are square pyramidal and square planar, and the Zn ions in 3 are square pyramidal and octahedral. The metal atoms in 2 and 3 are bridged by phenolate oxygen donors. The Mo ion in 4 is octahedral. The Schiff base ligand coordinates to the metal atoms through two phenolate O and two imino N donors. Biological assays revealed that the nickel and copper complexes have effective urease inhibition. [ABSTRACT FROM AUTHOR]

The current research reports the synthesis of a library of thiosemicarbazones (3-16) through a two-step chemical transformation. All the synthesized derivatives were purified and fully characterized through mass spectrometry, NMR spectroscopy (1H-, and 13C-NMR), and IR spectroscopy. All the members of the synthesized library were found to be new except compound 8. The synthesized library was screened for its inhibition potential against the urease enzyme. Almost all the compounds exhibited potent activity with the IC50 = 5.3 ± 0.8 − 15.5 ± 0.6 µM in comparison to the thiourea and acetohydroxamic acid used as standard (IC50 = 21.1 ± 0.2, 20.5 ± 0.4 µM). While significant activity was exhibited by compounds 14 and 15 with the IC50 = 23.6 ± 0.6 and 27.3 ± 1.2 µM. Furthermore, kinetic studies were carried out to determine the inhibition mode and molecular docking was employed to recognize the ligand-enzyme interactions. Thereby, the docking results are well in the direction of the in vitro results. Compounds ((E)-N-(2,5-dichlorophenyl)-2-(4-fluorobenzylidene)hydrazine-1-carbothioamide (3) and (E)-2-(2-chlorobenzylidene)-N-(2-fluorophenyl) hydrazinecarbothioamide (5) were identified as the most potent inhibitors of urease by both the in vitro and in silico studies. [ABSTRACT FROM AUTHOR]

A new tetranuclear copper(II) complex [Cu4L2(N3)2(CH3OH)2](NO3)2·4CH3OH (1) and a new trinuclear zinc(II) complex [Zn3L2(CH3COO)2] (2) have been prepared from the bis-Schiff base N,N'-bis(4-bromosalicylidene)-1,3-propanediamine (H2L) with copper nitrate and zinc acetate, respectively, in the presence of sodium azide. The complexes were characterized by elemental analysis, IR and UV-Vis spectroscopy. Molecular structures of both complexes were confirmed by single crystal X-ray determination. The Cu(II) atoms in complex 1 are bridged by phenolate oxygen atoms and end-on azide ligands. The Zn(II) atoms in complex 2 are bridged by phenolate oxygen atoms and acetate ligands. The Cu(II) atoms in complex 1 are in square planar and square pyramidal coordination. The Zn(II) atoms in complex 2 are in square pyramidal and octahedral coordination. The Schiff base ligand coordinates to the metal atoms through two phenolate O and two imino N atoms. The biological assay reveals that the copper(II) complex has effective urease inhibition. [ABSTRACT FROM AUTHOR]

The current research deals with the microwave-assisted green synthesis of two acridine-based libraries and in vitro urease inhibitory activities. The first library is based on 9-phenyl acridine 1–13 derivatives, while the second is based on 10H-acridin-9-one 14–33 derivatives. All compounds were characterized using FTIR, EI-MS, 1H-NMR, and CHNX techniques. As a result of in vitro evaluation of the synthesized derivatives, most compounds showed potent inhibitory activity against urease with IC50 values ranging from 0.91 to 11.84 µM. Thiourea was used as the standard (IC50 = 19.43 ± 0.18 µM). The structure–activity relationship (SAR) was established to identify key relationships between studied compounds' chemical structure and biological activity. The kinetic studies revealed a competitive mode of inhibition by the compounds. In addition, molecular docking and MD simulation studies were conducted to determine the different interactions between the ligands (compounds) and the enzyme's active site for the retention time of the ligand into the active pocket of the protein. Thus, it is well-known that inhibiting the urease enzyme activity effectively treats infections caused by Helicobacter pylori. This study has identified that these synthetic acridines may serve as promising lead candidates as urease inhibitors. [ABSTRACT FROM AUTHOR]

In this study, a new series of 3H-quinazoline-4-thione derivatives were synthesized under ultrasonic irradiation conditions with high yield in a short time. The new compounds were characterized by FT-IR,1H, and 13C NMR spectral data. The antiurease activities of all new compounds were tested according to the method by Weatherburn. The inhibition results with the 3H-quinazoline-4-thione ring compounds were compared with those of some previously synthesized 3H-quinazolin-4-ones. More effective results were found for most quinazolinethione compounds. All new synthesized compounds have effective urease inhibition activity. Especially, the compound 2-(4-nitrobenzyl)quinazoline-4(3H)-thione (2i) has the best inhibition results with IC50 = 1.6 ± 0.049 μg/mL. [ABSTRACT FROM AUTHOR]

Urease, a nickel-dependent enzyme found in various life forms, catalyzes urea breakdown, concluding nitrogen metabolism by generating ammonia and carbamate. This process causes a rise in pH, supports the survival of pathogens, and can lead to infections such as gastric disorders like ulcers and cancer in humans. Helicobacter pylori employs urease for survival in the acidic environment of the stomach and in protein synthesis. To treat such infections and inhibit the growth of pathogens, it is mandatory to obstruct urease activity; therefore, derivatives of 1-(3-nitropyridin-2-yl)piperazine were synthesized (5a-o; 7a-k). All these newly synthesized compounds were investigated for urease inhibition by in vitro inhibition assays. The results showed that 5b and 7e are the most active inhibitors, having IC50 values of 2.0 ± 0.73 and 2.24 ± 1.63 ^iM, respectively. These IC50 values are lower than the IC50 value of the standard thiourea, which was 23.2 ± 11.0 ^iM. The hemolysis potential of 5b, 5c, 5i, 7e, and 7h was also determined; 7e and 7h exhibited good biocompatibility in human blood cells. Through in silico analysis, it was shown that both these potent inhibitors develop favorable interactions with the active site of urease, having binding energies of -8.0 (5b) and -8.1 (7e) kcal/mol. The binding energy of thiourea was -2.8 kcal/mol. Moreover, 5b and 7e have high gastrointestinal permeability as predicted via computational analysis. On the other hand, the IC50 value and binding energy of precursor compound 3 was 3.90 ± 1.91 ^M and -6.1 kcal/mol, respectively. Consequently, 5b and 7e can serve as important inhibitors of urease. [ABSTRACT FROM AUTHOR]

Four samples of fir honeydew honey from Podkarpackie labeled with a Protected Designation of Origin symbol were tested in terms of their physicochemical parameters, antioxidant, and antibacterial effects, as well as their anti-migration properties against a breast cancer cell line (MCF-7) and fibroblasts. The results confirmed the high quality of tested samples regarding the obligatory parameters, as well as the additional indicators used (antioxidant and enzymatic activity), compared to representative rapeseed honey. Among the tested bacterial strains, the greatest effectiveness was demonstrated against Klebsiella pneumoniae and Streptococcus spp. Moreover, the results obtained in the urease inhibition in vitro test suggested the potential use of honeydew honey in the treatment of urease-positive bacterial infections. For the first time, using a scratch test it was found that the Podkarpackie honeydew honey efficiently affected the migration of cancer breast cells, whereas it only slightly inhibited the movement of normal fibroblasts. It can be suggested that the quality of honey guaranteed by the Protected Designation of Origin label could be the key factor of honeydew honey's bioactivity and its potential medicinal use. [ABSTRACT FROM AUTHOR]

Six new thiosemicarbazones were prepared and structurally characterized by elemental analysis, NMR and IR spectra and single-crystal X-ray diffraction. The compounds were evaluated for their Jack bean urease inhibitory activities. Among the compounds, those with hydroxyl and chloro substituent groups have effective activity with IC50 values of 1.8-12.7 µmol L-1. Docking simulations were performed to insert the molecules of the compounds into the active urease site determined by the crystal structure to determine their probable binding modes. [ABSTRACT FROM AUTHOR]

The presence of ammonium ions in urine, along with basic pH in the presence of urease-producing bacteria, promotes the production of struvite stones. This causes renal malfunction, which is manifested by symptoms such as fever, nausea, vomiting, and blood in the urine. The involvement of urease in stone formation makes it a good target for finding urease enzyme inhibitors, which have the potential to be developed as lead drugs against kidney stones in the future. The documented ethnopharmacology of coumarin 2-one against bacterial, fungal and viral strains encouraged us to synthesize new derivatives of coumarins by reacting aromatic aldehydes with 4-aminocoumarin. The synthesized compounds (2a to 11a) were evaluated for their antimicrobial, in vitro, and in silico properties against the urease enzyme. The study also covers in vivo determination of the synthesized compounds with respect to different types of induced ulcers. The molecular docking study along with extended MD simulations (100 ns each) and MMPBSA study confirmed the potential inhibitory candidates as evident from computed ∆Gbind (3a = −11.62 and 5a = −12.08 Kcal/mol) against the urease enzyme. The in silico analyses were augmented by an enzymatic assay, which revealed that compounds 3a and 5a had strong inhibitory action, with IC50 of 0.412 µM (64.0% inhibition) and 0.322 µM (77.7% inhibition), respectively, compared to standard (Thiourea) with 82% inhibition at 0.14 µM. Moreover, the most active compound, 5a, was further tested in vivo for antiulcer activity by different types of induced ulcers, including pyloric ligation-, ethanol-, aspirin-, and histamine-induced ulcers. Compound 5a effectively reduced gastric acidity, lipid peroxidation, and ulceration in a rat model while also inhibiting gastric ATPase activity, which makes it a promising candidate for ulcer treatment. As a result of the current research, 3a and 5a may be used as new molecules for developing potent urease inhibitors. Additionally, the compound 3a showed antibacterial activity against Staphylococcus aureus and Salmonella typhimurium, with zones of inhibition of 41 ± 0.9 mm and 35 ± 0.9 mm, respectively. Compound 7a showed antibacterial activity against Staphylococcus aureus and Salmonella typhimurium, with zones of inhibition of 30 ± 0.8 mm and 42 ± 0.8 mm, respectively. These results prove that the synthesized compounds also possess good antibacterial potential against Gram-positive and Gram-negative bacterial strains. [ABSTRACT FROM AUTHOR]

Hyperactivity of the urease enzyme leads to different pathologic conditions in humans, including gastric and peptic ulcers, urinary catheter incrustation, inflammation, adenocarcinoma, lymphoma, etc. Therefore, its inhibition is obligatory to combat these infections. This study demonstrates the assessment of in vitro urease inhibitory potential of synthetic 1,2,3-benzotriazoles 1‒40 followed by an in silico study to identify new and potential urease inhibitors. Good to moderate urease inhibitory activities were observed in the range of IC50 from 30.1±0.17 to 86.2±0.38 μM in comparison with thiourea as standard (IC50 = 21.5±0.47 μM). Several compounds with various substitutions on the benzotriazole and aryl rings were identified as significantly active urease inhibitors. Furthermore, molecular docking studies showed the possible binding interaction between urease enzymes and ligands (synthetic 1,2,3-benzotriazoles). There was a good correlation between the results of in silico and in vitro studies. [ABSTRACT FROM AUTHOR]

Furan chalcone scaffolds belong to the most privileged and promising oxygen-containing heterocyclic class of compounds, which have a wide spectrum of therapeutic applications in the field of pharmaceutics, pharmacology, and medicinal chemistry. This research described the synthesis of a series of twelve novel and seven reported furan chalcone (conventional synthetic approach) analogues 4a–s through the application of microwave-assisted synthetic methodology and evaluated for therapeutic inhibition potential against bacterial urease enzyme. In the first step, a series of nineteen substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a–s were achieved in moderate to good yields (40–70%). These substituted 5-aryl-2-furan-2-carbaldehyde derivatives 3a–s were condensed with acetophenone via Claisen–Schmidt condensation to furnish 19 substituted furan chalcone scaffolds 4a–s in excellent yields (85–92%) in microwave-assisted synthetic approach, while in conventional methodology, these furan chalcone 4a–s were furnished in good yield (65–90%). Furan chalcone structural motifs 4a–s were characterized through elemental analysis and spectroscopic techniques. These nineteen (19)-afforded furan chalcones 4a–s were screened for urease inhibitory chemotherapeutic efficacy and most of the furan chalcones displayed promising urease inhibition activity. The most active urease inhibitors were 1-phenyl-3-[5-(2′,5′-dichlorophenyl)-2-furyl]-2–propen-1-one 4h with an IC50 value of 16.13 ± 2.45 μM, and 1-phenyl- 3-[5-(2′-chlorophenyl)-2-furyl] -2-propen-1-one 4s with an IC50 value of 18.75 ± 0.85 μM in comparison with reference drug thiourea (IC50 = 21.25 ± 0.15 μM). These furan chalcone derivatives 4h and 4s are more efficient urease inhibitors than reference drug thiourea. Structure–activity relationship (SAR) revealed that the 2,5-dichloro 4h and 2-chloro 4s moiety containing furan chalcone derivatives may be considered as potential lead reagents for urease inhibition. The in silico molecular docking study results are in agreement with the experimental biological findings. The results of this study may be helpful in the future drug discovery and designing of novel efficient urease inhibitory agents from this biologically active class of furan chalcones. [ABSTRACT FROM AUTHOR]

Five copper(II), zinc(II) and nickel(II) complexes, [Cu2L2(μ1,1-N3)2] (1), [Zn2L2(μ2-η1:η1-CH3COO)(NCS)]EtOH (2), [Zn2L2(μ2-η1:η1-CH3COO)(N3)]MeOH (3), [Zn2Cl2L2] (4) and [NiL(HL)]ClO4 (5), were prepared from the Schiff base 3-methyl-2-((pyridin-2-ylmethylene)amino)phenol (HL). The compounds have been characterized by physico-chemical methods including elemental analysis, IR, and UV–Vis spectra. Structures of the five new complexes were determined by single crystal X-ray diffraction. The copper ions in 1 are in square pyramidal, while zinc ions in 2, 3, and 4 are distorted square pyramidal, and the nickel ions in 5 are octahedral. The biological assay indicated that zinc complex 2 has the most effective activity on Jack bean urease with IC50 = 1.7 ± 0.8 μmol·L−1. Molecular docking was performed to study the interaction between the active center of the urease with molecules of the complexes. [ABSTRACT FROM AUTHOR]

Three copper(II) and cobalt(III) complexes, [CuL(dca)]n (1), [CuL(N3)]n (2) and [CoL(N3)2(DMF)] (3), where L is the monoanionic form of the Schiff base (((2-(pyrrolidin-1-yl)ethyl)imino)methyl)naphthalen-2-ol (HL), and dca is dicyanamide, have been prepared and characterized by elemental analyses, IR and UV-Vis spectroscopy, as well as single crystal X-ray diffraction. The Cu atoms in complexes 1 and 2 are in square pyramidal coordination, and the Co atom in complex 3 is in octahedral one. Complexes 1 and 2 inhibit the Jack bean urease with IC50 values of 0.25 ± 0.14 and 0.32 ± 0.15 μmol L-1, respectively. Complex 3 show weak activity on Jack bean urease with percentage inhibition of 37%. [ABSTRACT FROM AUTHOR]

Omeprazole, a proton pump inhibitor, is used for gastric and duodenal ulcers, gastroesophageal reflux disease, Helicobacter pylori infection, etc. Current research is based on the loading of omeprazole on surface silver nanoparticles by chemical method. The appearance of an absorption peak at 421 nm confirmed the synthesis of nanoparticles. The FT-IR further confirmed the conjugation of functional groups present in omeprazole moiety with silver. The size and morphology were elucidated by transmission electron microscopy and X-ray diffraction which revealed a spherical shape with an average particle size of 16–20 nm. To know enhancement in their efficacy, the omeprazole-loaded nanoparticles were evaluated against antibacterial, urease inhibition, and antioxidant activities. Nanoparticles showed significant antibacterial potential against Staphylococcus aureus and Escherichia coli with 12 ± 0.41 and 13.6 ± 1.02 mm zones of inhibition, respectively. Almost 2.43 times enhanced urease inhibitory activity was found for nanoparticles (IC50 = 2.17 ± 0.10 µg·mL−1) as compared to omeprazole (IC50 = 5.28 ± 0.14 µg·mL−1). The radical scavenging activity of nanoparticles also increased significantly. The synthesized nanoparticles were docked in the active site of urease to investigate their binding mode. Due to excellent urease and bacterial inhibition, these nanoparticles can be used for ulcers.

In this present study, we have designed, synthetized twenty three tetra-substituted-imidazole-based fluorescent dyes that belongs to three different families of π-extended, π-fused, and non-fused tetra-substituted derivatives, to investigate their photophysical and biological properties namely anti-cancer and urease inhibitory activity. The impact of structural variation on photophysical properties, and their association with solvent’s polarity, and proticity were throughly examined by comparing with their analogues of blocked ESIPT functionality. Further, they were studied experimentally by means of absorption and fluorescence spectra monitoring through different solvent systems as well as theoretically by density functional theory/time dependent-density functional theory (DFT/TDDFT) calculations, respectively. For the evaluation of biological properties of imidazole molecules, urease inhibitory activity of the imidazole derivatives against urease protein 4H9M was investigated through docking and in vitro studies. Among the synthesized compounds, AHPI-Br and POMPI-F showed the most effective urease inhibitory activity with IC50 values of 0.0288 ± 0.0034 and 0.0289 ± 0.0025 μM and provided the highest docking scores. Moreover, anti-cancer activity of PHPI-I and PHPI-CI imidazole derivatives was confirmed by cytotoxic, and flurorescene analysis in stomach cancer cell lines (AGS). Our results demonstrated that PHPI-I, PHPI-Cl exhibited significant apoptotic mediated cell death compared to all other imidazole groups in both in vitro and in silico analysis. Our present study concluded that synthesis of imidazole derivatives have ability to inhibit urease enzyme activity and anti-cancer activity in vitro and can act as a potential therapeutic targets and warrants in vivo studies.

Background: Urease belongs to the family of amid hydrolases with two nickel atoms in their core structure. On the basis of literature survey, this research work is mainly focused on the study of bis-Schiff base derivatives of benzyl phenyl ketone nucleus. Objective: Synthesis of benzyl phenyl ketone based bis-Schiff bases in search of potent urease inhibitors. Method: In the current work, bis-Schiff bases were synthesized through two steps reaction by reacting benzyl phenyl ketone with excess of hydrazine hydrate in ethanol solvent in the first step to get the desired hydrazone. In last, different substituted aromatic aldehydes were refluxed in catalytic amount of acetic acid with the desired hydrazone to obtain bis-Schiff base derivatives in tremendous yields. Using various spectroscopic techniques including FTIR, HR-ESI-MS, and 1H NMR spectroscopy were used to clarify the structures of the created bis-Schiff base derivatives. Results: The prepared compounds were finally screened for their in-vitro urease inhibition activity. All the synthesized derivatives (3–9) showed excellent to less inhibitory activity when compared with standard thiourea (IC50 = 21.15 ± 0.32 µM). Compounds 3 (IC50 = 22.21 ± 0.42 µM), 4 (IC50 = 26.11 ± 0.22 µM) and 6 (IC50 = 28.11 ± 0.22 µM) were found the most active urease inhibitors near to standard thiourea among the synthesized series. Similarly, compound 5 having IC50 value of 34.32 ± 0.65 µM showed significant inhibitory activity against urease enzyme. Furthermore, three compounds 7, 8, and 9 exhibited less activity with IC50 values of 45.91 ± 0.14, 47.91 ± 0.14, and 48.33 ± 0.72 µM respectively. DFT used to calculate frontier molecular orbitals including; HOMO and LUMO to indicate the charge transfer from molecule to biological transfer, and MEP map to indicate the chemically reactive zone suitable for drug action. The electron localization function (ELF), non-bonding orbitals, AIM charges are also calculated. The docking study contributed to the analysis of urease protein binding.

Phytochemical investigation of dried flower buds of Syzygium aromaticum (L.) Merr. & L.M.Perry. (clove) led to the isolation and identification of fourteen known compounds, oleanolic acid (1), betulinic acid (2), para methyl benzoic acid (3), sabrinic acid (4) eucalyptolic acid (5), nigricin (6), 3-O-trans-para-coumaroylmaslinic acid (7), methyl maslinate (8), maslinic acid (9), 3, 4, 5-trimethoxy-3′,4′-O,O-methylideneflavellagic acid (10), lantanone (11) 3,4,3′-trimethoxyellagic acid (12), 11-oxo-oleanolic acid (13), and β-sitosterol-3-O-β-D-glucopyranoside (14). Their structures were identified by 1H NMR, 13C NMR, Mass spectroscopic techniques, and comparison with the literature data. Compounds 3, and 7–9 showed a strong mortality against root knot nematode, Meloidogyne incognita at 0.125% concentration after 72 hours (88–92% inhibition). Compound 4 showed a good anti-glycation activity with IC50 = 142.0 ± 1.8 µM when compared with standard, i.e. rutin (IC50 = 54.59 ± 2.20 µM). Compound 10 showed a comparable urease inhibitory activity (IC50 = 26.1 ± 0.19 µM) with the positive control thiourea (IC50 = 24.5 ± 0.34 µM). [ABSTRACT FROM AUTHOR]

Many heterocycles have been developed as drugs due to their capacity to interact productively with biological systems. The present study aimed to synthesize cocrystals of the heterocyclic antitubercular agent pyrazinamide (PYZ, 1, BCS III) and the commercially available anticonvulsant drug carbamazepine (CBZ, 2, BCS class II) to study the effect of cocrystallization on the stability and biological activities of these drugs. Two new cocrystals, namely, pyrazinamide–homophthalic acid (1/1) (PYZ:HMA, 3) and carbamazepine–5‐chlorosalicylic acid (1/1) (CBZ:5‐SA, 4), were synthesized. The single‐crystal X‐ray diffraction‐based structure of carbamazepine–trans‐cinnamic acid (1/1) (CBZ:TCA, 5) was also studied for the first time, along with the known cocrystal carbamazepine–nicotinamide (1/1) (CBZ:NA, 6). From a combination drug perspective, these are interesting pharmaceutical cocrystals to overcome the known side effects of PYZ (1) therapy, and the poor biopharmaceutical properties of CBZ (2). The purity and homogeneity of all the synthesized cocrystals were confirmed by single‐crystal X‐ray diffraction, powder X‐ray diffraction and FT–IR analysis, followed by thermal stability studies based on differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Detailed intermolecular interactions and the role of hydrogen bonding towards crystal stability were evaluated quantitatively via Hirshfeld surface analysis. The solubility of CBZ at pH 6.8 and 7.4 in 0.1 N HCl and H2O were compared with the values of cocrystal CBZ:5‐SA (4). The solubility of CBZ:5‐SA was found to be significantly improved at pH 6.8 and 7.4 in H2O. All the synthesized cocrystals 3–6 exhibited a potent urease inhibition (IC50 values range from 17.32 ± 0.89 to 12.3 ± 0.8 µM), several times more potent than standard acetohydroxamic acid (IC50 = 20.34 ± 0.43 µM). PYZ:HMA (3) also exhibited potent larvicidal activity against Aedes aegypti. Among the synthesized cocrystals, PYZ:HMA (3) and CBZ:TCA (5) were found to possess antileishmanial activity against the miltefosine‐induced resistant strain of Leishmania major, with IC50 values of 111.98 ± 0.99 and 111.90 ± 1.44 µM, respectively, in comparison with miltefosine (IC50 = 169.55 ± 0.20 µM).The current study demonstrates the cocrystallization of pyrazinamide with homophthalic acid employing the reflux method, and the cocrystallization of the commercially available heterocyclic drug carbamazepine with 5‐chlorosalicylic acid, trans‐cinnamic acid and nicotinamide. The synthesized cocrystals were characterized by FT–IR, PXRD and SC‐XRD techniques, followed by thermal stability studies based on DSC and TGA analysis. [ABSTRACT FROM AUTHOR]

Main chemical compositions of essential oil (EO) from Litsea cubeba fruit collected in Kon Tum Province of Vietnam were geranial (32.0%), neral (24.3%), citronellal (14.2%), and limonene (10.1%). Twenty-four compounds of the EO were identified and compared with those from EOs previously reported in India, China, and Malaysia. Minimal inhibitory and bactericidal concentrations (MIC and MBC) indicated that the EO induced high levels of growth inhibition and moderate bactericidal activity against seven test Helicobacter pylori strains, including six strains resistant to one to four antibiotics, azithromycin, erythromycin, levofloxacin, and metronidazole. The bacterial biofilm formation was significantly suppressed by the EO at 1/2 and 3/4×MIC. The EO also exerts inhibitory activity against H. pylori-urease and convert a spiral form of H. pylori into a coccoid form. Fruit EO inhibits bacterial growth via both contact and fumigant action. [ABSTRACT FROM AUTHOR]

Cu(II) complexes of substituted Guanidines having common formula [κ2(O, N)-C6H5CONHC(NHR1)NR2]2Cu(II), in which R1 = C6H5– and R2 = C(CH3)3 (1), CH2CH2CH3 (2), CH(CH3)2 (3), 2, 6-Cl2C6H3 (4) and 4-CH3C6H4 (5) were synthesized and their structural and chemical characteristics were examined by CHN analyzer, FTIR, NMR Spectrometer (including 1H and 13C) and magnetic susceptibility balance. Two of the guanidine ligands and their Cu(II) complexes were also analyzed by single crystal X-ray diffraction. The X-ray diffraction analysis revealed that majority of the studied guanidine ligands were stable due to intermolecular and intra-molecular hydrogen bonding. The synthesized compounds are mononuclear having pseudo square planar geometry, whereas guanidine ligands attached to the metal center via oxygen and nitrogen atoms. The metallodrugs demonstrated better urease inhibition action than their parent guanidine ligands and also have shown fairly good score regarding the potato disk bioassay in comparison with the vincristine, employed as a standard drug. [ABSTRACT FROM AUTHOR]

Three mononuclear copper(II) and nickel(II) complexes, [Cu(L1)(NCS)(CH3OH)] (1), [Cu(L2)(NCS)] (2) and [Ni(L2)(N3)] (3), where L1 and L2 are the monoanionic forms of the Schiff bases N'-(pyridin-2-ylmethylene)picolinohydrazide (HL1) and 4-methyl-2-(((pyridin-2-ylmethyl)imino)methyl)phenol (HL2), have been prepared and characterized by elemental analysis, IR and UV-Vis spectroscopy, as well as single crystal X-ray diffraction studies. The Cu atom in complex 1 is in a square pyramidal coordination, with the three N atoms of the ligand L and the N atom of the thiocyanate ligand in the basal plane, and with the methanol O atom at the apical position. The Cu and Ni atoms in complexes 2 and 3 are in square planar coordination, with the three donor atoms of the Schiff base ligands and the terminal N atoms of thiocyanate and azide ligands. Complexes 1 and 2 inhibit the Jack bean urease with IC50 value of 0.33±0.12 and 0.39±0.10 μmol L–1, respectively. Molecular docking study was performed to investigate the interaction between the complexes and the enzyme.

A pair of structurally similar dicyanamide bridged copper(II) and zinc(II) complexes [CuL(dca)]n (1) and [ZnL(dca)]n (2), were prepared from the fluorine containing Schiff base 5-fluoro-2-(((2-hydroxyethyl)imino)methyl)phenol (HL). The compounds were characterized by physico-chemical methods. Structures of the complexes were confirmed by single crystal X-ray diffraction. The Cu atom in complex 1 is in square pyramidal coordination, whereas the Zn atom in complex 2 is in trigonal bipyramidal coordination. The copper complex has effective Jack bean urease inhibitory activity, with IC50 value of 0.14±0.12 μmol L–1. 搜索 复制

Four samples of fir honeydew honey from Podkarpackie labeled with a Protected Designation of Origin symbol were tested in terms of their physicochemical parameters, antioxidant, and antibacterial effects, as well as their anti-migration properties against a breast cancer cell line (MCF-7) and fibroblasts. The results confirmed the high quality of tested samples regarding the obligatory parameters, as well as the additional indicators used (antioxidant and enzymatic activity), compared to representative rapeseed honey. Among the tested bacterial strains, the greatest effectiveness was demonstrated against Klebsiella pneumoniae and Streptococcus spp. Moreover, the results obtained in the urease inhibition in vitro test suggested the potential use of honeydew honey in the treatment of urease-positive bacterial infections. For the first time, using a scratch test it was found that the Podkarpackie honeydew honey efficiently affected the migration of cancer breast cells, whereas it only slightly inhibited the movement of normal fibroblasts. It can be suggested that the quality of honey guaranteed by the Protected Designation of Origin label could be the key factor of honeydew honey’s bioactivity and its potential medicinal use.

Bis-acyl-thiourea derivatives, namely N,N'-(((4-nitro-1,2-phenylene)bis(azanediyl)) bis(carbonothioyl))bis(2,4-dichlorobenzamide) (UP-1), N,N'-(((4-nitro-1,2-phenylene) bis(azanediyl))bis(carbonothioyl))diheptanamide (UP-2), and N,N'-(((4-nitro-1,2-phenylene)bis(azanediyl))bis(carbonothioyl))dibutannamide (UP-3), were synthesized in two steps. The structural characterization of the derivatives was carried out by FTIR, 1H-NMR, and 13C-NMR, and then their DNA binding, anti-urease, and anticancer activities were explored. Both theoretical and experimental results, as obtained by density functional theory, molecular docking, UV-visible spectroscopy, fluorescence (Flu-)spectroscopy, cyclic voltammetry (CV), and viscometry, pointed towards compounds' interactions with DNA. However, the values of binding constant (Kb), binding site size (n), and negative Gibbs free energy change (ΔG) (as evaluated by docking, UV-vis, Flu-, and CV) indicated that all the derivatives exhibited binding interactions with the DNA in the order UP-3 > UP-2 > UP-1. The experimental findings from spectral and electrochemical analysis complemented each other and supported the theoretical analysis. The lower diffusion coefficient (Do) values, as obtained from CV responses of each compound after DNA addition at various scan rates, further confirmed the formation of a bulky compound–DNA complex that caused slow diffusion. The mixed binding mode of interaction as seen in docking was further verified by changes in DNA viscosity with varying compound concentrations. All compounds showed strong anti-urease activity, whereas UP-1 was found to have comparatively better inhibitory efficiency, with an IC50 value of 1.55 ± 0.0288 µM. The dose-dependent cytotoxicity of the synthesized derivatives against glioblastoma MG-U87 cells (a human brain cancer cell line) followed by HEK-293 cells (a normal human embryonic kidney cell line) indicated that UP-1 and UP-3 have greater cytotoxicity against both cancerous and healthy cell lines at 400 µM. However, dose-dependent responses of UP-2 showed cytotoxicity against cancerous cells, while it showed no cytotoxicity on the healthy cell line at a low concentration range of 40–120 µM. [ABSTRACT FROM AUTHOR]

Thiosemicarbazones are biological active compounds. In this work, five new thiosemicarbazones were prepared and structurally characterized by elemental analysis, 1H NMR and IR spectra, as well as single crystal X-ray diffraction. The compounds were evaluated for their urease inhibitory activities. Among the compounds, those with hydroxyl substituent groups have effective activity with IC50 values of 1.5-2.3 μmol/L. Docking simulation was performed to insert the molecules of the compounds into the crystal structure of Jack bean urease at the active site to determine their probable binding modes. [ABSTRACT FROM AUTHOR]

A new series of benzimidazoles including triazole and thiosemicarbazide moieties was synthesized and their urease inhibition studies were evaluated according to the method of Van Slyke and Archibald. Especially triazole derivatives have effective inhibition activities between 0.04±0.026 and 0.26±0.042 µM IC50 values. The best antiurease activities with IC50 0.04±0.026 and 0.06±0.033 µM belongs to 5-[(5,6-dichloro-1H-benzimidazol-1-yl)methyl]-4-nitrophenyl-4H-1,2,4-triazole-3-thiol and 2-[(2-benzyl-5,6-dichloro-1H-benzimidazol-1-yl)acetyl]-N-(4-nitrophenyl)hydrazinecarbothioamide, respectively. [ABSTRACT FROM AUTHOR]

Recently, screening of efficient urease inhibitors by employing organic small molecules metalloderivatives interests the scientific community due to their efficacy for treatment of urease triggered health complications. This study comprises the synthesis, urease inhibition activity, optical analysis and molecular modeling of hydrazinecarbothioamide and hydrazinecarboxamide metalloderivatives. Characterization of synthesized materials was done by UV-visible, fluorescence, NMR and FTIR spectroscopic analysis. Metalloderivatization of ligands induce increment in urease inhibition potential and effect was prominent for copper complexes with 10-fold enhancement, cobalt complex with 3.5 fold's enhancement and palladium with 2-fold increment in the inhibition efficacy toward urease when it was compared with reference urease inhibitor. Zinc and iron complexes cause declined urease inhibition activity of the bare ligand. The overall activity of hydrazinecarbothioamide slightly exceeds than that of hydrazinecarboxamide, possibly due to larger complexation ability of sulfur-based ligand in comparison to oxygenated derivatives i.e., hydrazinecarboxamide. The enzyme inhibition kinetics for the most active complexes represent the mixed type urease inhibition for 3a and competitive urease inhibition for 5a, as determined by Lineweaver–Burk plots. The docked scoring values for both the ligands were calculated to be 61.34, 64.72, 56.68, 62.94, 64.98 and 58.98. Three active hydrogen bonds were observed in docking complex upon computational analysis of most potent metallodrug 3a inside active region of targeted protein. [ABSTRACT FROM AUTHOR]

Three new zinc(II) complexes, [Zn3(µ2-η¹:η¹-OAc)2(µ2-η2:η0-OAc)2L2] (1), [Zn3(µ2-η¹:η¹-OAc)2(µ1,1-N3)(N3)L2] (2), [Zn2(µ1,3-N3)(N3)(H2O)L2] (3), with the Schiff base ligand 4-chloro-2-(((2-(pyrrolidin-1-yl)ethyl)imino)methyl)phenol (HL) have been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopic studies. Crystal structures of the complexes were confirmed by single crystal X-ray diffraction. Complex 1 is a bidentate acetato, monoatomic bridging acetato, and phenolato co-bridged trinuclear zinc compound. The Zn atoms are in octahedral and square pyramidal coordination. Complex 2 is a bidentate acetato, end-on azido, and phenolato co-bridged trinuclear zinc compound. The Zn atoms are in trigonal bipyramidal and square pyramidal coordination. Complex 3 is an end-to-end azido bridged dinuclear zinc compound. The Zn atoms are in square pyramidal and trigonal bipyramidal coordination. The Schiff base ligands in the complexes coordinate to the Zn atoms through the phenolate oxygen, imino nitrogen and pyrrolidine nitrogen. The complexes have interesting inhibitory activity on Jack bean urease, with IC50 values of 7.1-15.3 µmol·L-1. [ABSTRACT FROM AUTHOR]

Several S-substituted-2-mercaptobenzimidazole derivatives 1–34 were synthesized by reacting 2-mercaptobenzimidazole with a variety of substituted benzyl bromide and characterized with the help of various spectroscopic techniques. All synthetic compounds were evaluated for urease inhibitory and DPPH radical scavenging activities. Compounds showed significant to moderate urease inhibitory activity in the range of IC50 = 16.8 ± 0.76–74.3 ± 0.72 µM, in comparison with the standard thiourea (IC50 = 22.4 ± 0.29 µM). It is worth stating that all molecules exhibited noteworthy DPPH radical scavenging potential with IC50 values of 15.5 ± 0.58 to 89.3 ± 0.12 µM when compared with the standard butylated hydroxy anisole BHA (IC50 = 44.2 ± 0.45 µM). A structure–activity relationship (SAR) was presented by analyzing the impact of varying substitutions on urease inhibitory potential. A molecular docking study was done to streamline the binding interactions of ligands (synthetic molecules) with the active pocket of urease enzyme. In addition, cytotoxicity of the most potent compounds 1–4, 14, 18, 20, 28, and 32, was also evaluated, and all were found to be non-cytotoxic. [ABSTRACT FROM AUTHOR]

Introduction: Helicobacter pylori is Gram-negative helical bacteria that inhibit stomach mucosal lining and establish infection. Urease enzyme was confirmed to be pivotal target in which its suppression will prompt bacteria treatment and eradication. Methods: Series of naturally bioactive compounds were selected based on ethnobotanical and molecular modeling techniques with potential urease inhibitory effect. The selected phytochemical compounds were in-silico and in-vitro assayed against urease enzyme, minimal inhibitory concentrations (MIC) and a synergistic effect was studied and cultured specifically for H. pylori. Results: Terpineol was considered as the most active compound with an IC50 of 1.443 μg/ml (R2 = 0.9374). The synergistic effect of terpineol and metronidazole indicated a possible additive effect (fractional inhibitory concentration result is 0.78) with improvement of MIC results for both terpineol and metronidazole. Conclusion: This study suggests that terpineol is best to be considered as a lead compound for H. pylori infection treatment and could be a potent inhibitor when combined with metronidazole targeting urease enzyme.

Abstract Cashmirins A (1) and B (2), new prenylated coumarins, have been isolated from the EtOAc- soluble fraction of the whole plant of Sorbus cashmiriana Hedlung, Monog. along with seselin (3), scopoletin (4), 3-hydroxyxanthyletin (5) and luteolin (6), reported for the first time from this species. Their structures were elucidated by spectroscopic techniques including MS, 1D and 2D NMR spectroscopy. Both new compounds 1 and 2 were investigated for biological activities and showed significant antifungal and urease inhibitory activities. Compounds 1 and 2 exhibited significant activity against Aspergillus flavus, Macrophomina phaseolina, Trichophyton simii, Trichophyton schoenleinii, and Pseudallescheria boydri. Both compounds also exhibited significant inhibitory activity against Jack bean urease with IC50 values of 28.2±0.12 µM and 30.3±0.18 µM, respectively compared to thiourea used as positive control.

In current work, three N-acetyl pyrazoline derivatives (1–3) have been prepared via 1,4-addition reaction of hydrazine on chalcones, followed by cyclization of the adduct in the presence of acetic acid. The structural interpretation of synthesized compounds was accomplished using various characterization techniques like FT-IR, Ultraviolet/visible spectroscopy, 1H NMR and 13C NMR. The synthesized compounds were evaluated for antioxidant, Urease inhibitory and Lipoxygenase inhibitory activities and results revealed that compound 2 showed promising antioxidant, Urease inhibitory and Lipoxygenase inhibitory activity with IC50 values 33.2 ± 0.45, 32.7 ± 0.11 and 42.2 ± 0.77, respectively. Moreover, DNA binding interactions of the N-acetyl pyrazoline derivatives have also been carried out with SS-DNA (Salmon Sperm DNA) using absorption spectroscopy. Furthermore, molecular docking was conducted for a ready comparison with the experimental data and to determine the interactions involved. ADMET profiling of pyrazoline derivatives was also done using Admet SAR. Besides that, quantum chemical calculations using DFT (density functional theory) were carried out to explore optimized geometries, FMOs (Frontier molecular orbitals), NBOs (Nonbonding orbitals) of synthesized compounds and to predict their NLO (Nonlinear optical) properties. The synthesized compounds showed much better NLO behavior than standard Urea along with a strong agreement between computed and empirically recorded spectral data.

Two biologically active adamantane-linked hydrazine-1-carbothioamide derivatives, namely 2-(adamantane-1-carbonyl)-N-(tert-butyl)hydrazine-1-carbothioamide) 1 and 2-(adamantane-1-carbonyl)-N-cyclohexylhydrazine-1-carbothioamide 2, have been synthesized. X-ray analysis was conducted to study the effect of the t-butyl and cyclohexyl moieties on the intermolecular interactions and conformation of the molecules in the solid state. X-ray analysis reveals that compound 1 exhibits folded conformation, whereas compound 2 adopts extended conformation. The Hirshfeld surface analysis indicates that the contributions of the major intercontacts involved in the stabilization of the crystal structures do not change much as a result of the t-butyl and cyclohexyl moieties. However, the presence and absence of these contacts is revealed by the 2D-fingerprint plots. The CLP–Pixel method was used to identify the energetically significant molecular dimers. These dimers are stabilized by different types of intermolecular interactions such as N–H···S, N–H···O, C–H···S, C–H···O, H–H bonding and C–H···π interactions. The strength of these interactions was quantified by using the QTAIM approach. The results suggest that N–H···O interaction is found to be stronger among other interactions. The in vitro assay suggests that both compounds 1 and 2 exhibit urease inhibition potential, and these compounds also display moderate antiproliferative activities. Molecular docking analysis shows the key interaction between urease enzyme and title compounds. [ABSTRACT FROM AUTHOR]

Soil urease inhibition slows down the urea hydrolysis and prolongs nitrogen (N) stay in soil, resulting in an increased N uptake by plants. Apart from several chemical urease inhibitors, the urease inhibition potential of plant extracts is rarely reported. In our previous study, the soil urease inhibition by Vachellia nilotica leaf extract was reported; however, its role in relation to growth and yield of wheat (Triticum aestivum) under pot and field conditions remains unknown. The acetonic extracts of 10, 20, and 50 g Vachellia nilotica leaves were given code names viz. Vn.Fl-10, Vn.Fl-20 and Vn.Fl-50, respectively, and coated on 100 g of urea individually. The enhancements of growth (total number of tillers, number of productive tillers, number of spikelets per spike, number of grains per spike, and 1000-grains weight) and yield (biological yield, straw yield, and grain yield) parameters of wheat by Vn.Fl-20 and Vn.Fl-50 coated urea treatments were compared with uncoated urea in a pot experiment. The experiment indicated that the Vachellia nilotica extract coatings were effective at improving N persistence in soil, as reflected by increased grain and straw N concentrations as well as uptakes. The reproduction of the aforementioned results, at the half and full recommended dose of urea under field conditions, reconfirmed the effectiveness of Vachellia nillotica coatings. Moreover, the Vn.Fl-20 and Vn.Fl-50 coated urea, at the half as well as full recommended dose under field conditions, proved equally effective in terms of higher biological, straw, and grain yield, and grain N uptake. The increments in the total number of tillers, number of productive tillers, 1000-grain weight, biological yield, straw yield, grain yield, grain N concentration, grain N-, and straw N uptake along with nitrogen use efficiency (NUE) components, i.e. nitrogen partial factor productivity (NPFP), nitrogen agronomic efficiency (NAE), partial nitrogen balance (PNB), and nitrogen recovery efficiency (NRE) of wheat highlighted the superiority of Vn.Fl-20 coating over the hydroquinone (Hq) coating on urea at the full recommended dose under field conditions. Given the findings of this study, Vachellia nilotica leaf extract coating (Vn.Fl-20) can be used as a natural urease inhibitor to reduce urea hydrolysis and enhance wheat productivity. [ABSTRACT FROM AUTHOR]