Search

Heterocyclic compounds containing nitrogen together with an oxygen atom in their structures are an important class of medicinal chemistry compounds due to their interesting diverse biological applications. Some compounds including carbazole ring, which are aromatic organic compounds in tricyclic structure, show biological activity in a wide spectrum. Oxadiazole compounds attract the attention of many chemists thanks to their antibacterial, antitumor, anticancer, anti-viral, antimicrobial, anti-HIV, antituberculosis and antioxidant properties. In this study, new oxadiazole substituted carbazole derivatives were synthesized and their antioxidant, antiurease activities were investigated. 9H-carbazole is a good starting material for the synthesis of carbazole derivatives. The antioxidant and antiurease activities of synthesized oxadiazole substituted new carbazole derivatives were investigated. Antioxidant activity methods such as DPPH (1,1’-diphenyl-2-picrylhydrazyl), ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt) radical scavenging activities and iron reducing power capacities were used to determine antioxidant activity of the compounds. All synthesized carbazole compounds showed antioxidant and antiurease activity. While compound 4 shows the strongest enzyme inhibition activity, the least active compound was found 5. All tested compounds showed higher enzyme inhibition activity than thiourea. The highest and the lowest antioxidant activities were observed as compounds 3 and 6, respectively. DOI: http://dx.doi.org/10.5281/zenodo.6612440

Heterocyclic compounds containing nitrogen together with an oxygen atom in their structures are an important class of medicinal chemistry compounds due to their interesting diverse biological applications. Some compounds including carbazole ring, which are aromatic organic compounds in tricyclic structure, show biological activity in a wide spectrum. Oxadiazole compounds attract the attention of many chemists thanks to their antibacterial, antitumor, anticancer, anti-viral, antimicrobial, anti-HIV, antituberculosis and antioxidant properties. In this study, new oxadiazole substituted carbazole derivatives were synthesized and their antioxidant, antiurease activities were investigated. 9H-carbazole is a good starting material for the synthesis of carbazole derivatives. The antioxidant and antiurease activities of synthesized oxadiazole substituted new carbazole derivatives were investigated. Antioxidant activity methods such as DPPH (1,1'-diphenyl-2-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt) radical scavenging activities and iron reducing power capacities were used to determine antioxidant activity of the compounds. All synthesized carbazole compounds showed antioxidant and antiurease activity. While compound 4 shows the strongest enzyme inhibition activity, the least active compound was found 5. All tested compounds showed higher enzyme inhibition activity than thiourea. The highest and the lowest antioxidant activities were observed as compounds 3 and 6, respectively. [ABSTRACT FROM AUTHOR]

Proteus mirabilis is a significant cause of urinary tract infection that may contribute to struvite stones. Anti-infection of this bacterium and anti-struvite formation must be considered. Sida acuta Burm. F. (SA) has been used for the treatment of diseases related to kidneys. Therefore, we investigated the effects of the SA leaf ethanolic extract (SAEE) on growth and on virulent factors (swarming motility and urease activity) of Proteusmirabilis isolated from kidney stone formers. We also evaluated anti-struvite crystal formation and phytochemical constituents of SAEE. The minimum inhibitory concentrations (MICs) of SAEE against three clinical P. mirabilis isolates were 8 mg/mL. Intriguingly, the 1/2MIC of SAEE had significant inhibitory effects on the swarming motility and urease activity of clinical P. mirabilis isolates when compared with the condition without SAEE. The SAEE at the various concentrations significantly inhibited the average weights of struvite crystals in a dose-dependent manner, compared with the control. The phytochemical analysis revealed that SAEE contained catechin, chlorogenic acid, rutin, and ferulic acid. This study indicated that SAEE has anti-P. mirabilis and anti-struvite crystal activities via its bioactive compounds. For this reason, SAEE may be developed as a new agent for the treatment of struvite stone induced by P. mirabilis.

[Display omitted] • Novel copper(II) complexes with Schiff-base ligands derived from 2-formylphenoxyacetic acid (fphaa) and DL-α-alanine, β-alanine, taurine, and γ-aminobutanoic acid. • New type of stereoisomerism arising from a different molecular arrangement of the apical ligand in square-pyramidal or square-bipyramidal complexes with respect to the conformation of a multidentate equatorial ligand. • Complexes with excellent inhibitory properties against jack bean urease. Enzyme urease plays a significant role in the pathogenesis of several diseases and has practical implications in fields such as agriculture and chemical analysis. Four new copper(II) complexes with Schiff-base ligands obtained from the template synthesis of 2-formylphenoxyacetic acid (fphaa) with DL-α-alanine, β-alanine, taurine, and γ-aminobutanoic acid were synthesized in addition to the previously described [Cu(fphaa-gly)(H 2 O)] derived from glycine. Crystallographic study of two solvates of Cu(fphaa-α-ala)⋅S (where S = H 2 O or DMSO) showed similarity of these complexes with the one derived from glycine. In addition, an E / Z isomerism originating in a different molecular arrangement of the aqua ligand with respect to the methyl group from alanine was described in the aqua complex. Only Z isomers were found in the complex with DMSO. All prepared complexes showed excellent inhibitory properties against jack bean urease (IC 50 = 0.53–0.71 μmol/dm3), considerably better than the standard inhibitor acetohydroxamic acid (IC 50 = 185 μmol/dm3). [ABSTRACT FROM AUTHOR]

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

Abstract: In this study, 1‐(4‐substitued benzyl)‐3,5‐diphenyl‐1H‐1,2,4‐triazoles (2 a‐e) and ethyl(3,5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)acetate (3) were synthesized starting from 3,5‐diphenyl‐1H‐1,2,4‐triazole (1). The ethyl acetate derivative (3) was converted to 2‐(3,5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)acetohydrazide (4) in ethanolic medium with hydrazine hydrate. The reaction of the acetohydrazide (4) with suitable isothiocyanates generate 2‐[(3, 5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)acetyl]‐4‐methyl/phenyhlthiosemicarbazide (5 a,b). The cyclization of the thiosemicarbazide (5 a,b) in the presence of NaOH (2 M) resulted in the formation of 5‐[(3, 5‐diphenyl‐1H‐1,2,4‐triazole‐1‐yl)methyl]‐4‐methyl/phenyl‐2,4‐dihidro‐3H‐1,2,4‐triazole‐3‐thiol (6 a,b). Finally, the synthesized 1,2,4‐triazole‐3‐thiols (6 a,b) were converted to their S‐substituebenzyl derivatives (7 a‐j). All of the synthesized compounds (1‐7) were also examined for antioxidant capacities, and antiurease and anti‐acetylcholinesterase (anti‐AChE) activities. It has been found that antioxidant capacity and anti‐urease activity of the compound 7 f is very good in biochemically active compounds. [ABSTRACT FROM AUTHOR]

Mannich base 1-[(4-methoxyphenyl)(2-methylidenecyclohexyl)methyl]pyrrolidine (MMP) was synthesized by condensing cyclohexanone, 4-methoxybenzaldehyde, and pyrrolidine together using ethanol as solvent. The synthesized ligand was further made to react with CuCl2, NiCl2, CoCl2, and FeCl2 to afford their respective complexes. Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), carbon thirteen nuclear magnetic resonance (13C NMR), thermogravimetric analysis (TGA), and mass spectrometry (MS) were used to characterize the ligand and its complexes. The proposed geometries of the complexes were established on the basis of metal-ligand ratio through atomic absorption spectroscopy (AAS). The synthesized compounds were analyzed for their antiurease potential. Mannich base showed moderate antiurease activity with an IC50 value of 224.83 ± 0.84 μM. Complexes with Ni (II) and Fe (II) exhibited potent antiurease activity (4.41 ± 0.003, 5.21 ± 0.003 μM, respectively) while the Co (II) complex showed excellent (46.52 ± 0.05 μM) antiurease activity and poor antiurease activity was shown by the Cu (II) complex (424.32 ± 0.96 μM) as compared with the standard thiourea (21.25 ± 0.15 μM). Docking studies of the ligand were also consistent with the experimental results. [ABSTRACT FROM AUTHOR]

A new series of benzimidazole compounds including hydrazinecarbothioamide, 1,2,4-triazole, 1,3,4-oxadiazole and imine function were synthesized starting from 5,6-dichloro-2-cyclopropyl-1 H -benzimidazole. All of the benzimidazole derivatives exhibited good urease inhibitor activity. Compound 6a proved to be the most potent showing an enzyme inhibitory activity with an IC 50 = 0.06 µM. Molecular docking studies were also conducted on enzyme extracted from Jack bean urease to identify the binding mode of the newly synthesized compounds. [ABSTRACT FROM AUTHOR]

Study was planned to evaluate urease inhibitory efficacy of aqueous-ethanol extract of medicinal plants including Mentha piperita, Violo odorata, Trachyspermum copticum, Metricarea chamomile and Foeniculum vulgare, traditionally used for management of gastrointestinal disorders. Phenol hypochlorite method was adopted to evaluate the urease inhibitory efficacy. The extracts were also phytochemically evaluated. The results showed that aqueous-ethanol extract of Mentha piperita, Violo odorata, Trachyspermum copticum, Metricarea chamomile and Foeniculum vulgare exhibited significant antiurease efficacy. The IC50 values of Mentha piperita, Metricarea hamomile, Foeniculum vulgare and Violo odorata extracts were 124±0.71, 119± 0.65, 119± 0.65 495±0.80 and 333±0.98 μg/ml respectively. Extract of Mentha piperita showed more antiurease potential in comparison to other plants extracts. Phytochemical screening of the extracts revealed the presence of alkaloids, tannins, saponins, flavonoids, flavones and sterol. The present study therefore, showed that the medicinal plants exhibit antiurease activity. [ABSTRACT FROM AUTHOR]

An efficient synthesis of new A-2 , A-3 , and A-4 analogues from amlodipine ( A-1 ) has been achieved. All synthesized compounds were investigated by elemental analysis, FTIR, EIMS, and 1 H NMR techniques. Crystal structures of A-2 and A-3 were determined by single crystal X-ray diffraction method. Compound A-2 crystallizes in a monoclinic space group C 2/ c having unit cell parameters a = 23.8754(9) Å, b = 8.6725(3) Å, c = 30.5777(12) Å, β = 90.673(2)°, and V = 6331.0(4) Å 3 , whereas A-3 crystallizes in a triclinic space group P 1 ¯ having unit cell parameters a = 8.2968(3) Å, b = 9.3112(4) Å, c = 18.1359(7) Å, α = 100.692(2)°, β = 98.316(3)°, γ = 102.747(2)°, and V = 1317.39(9) Å 3 . These compounds showed that C–H⋯O and N–H⋯O hydrogen bonds stabilize the crystal packing. The results of thermal analysis of all products were consistent with the proposed stoichiometry and compounds were found thermally stable up to 200 °C. The compounds were tested for direct free radical scavenging effect toward α, α-Diphenyl-1-picryl hydrazide (DPPH • ) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS •+ ) radical cation in aqueous phosphate-buffered saline of pH 7.4 and showed significant in vitro antioxidant potential. Antiurease activity was also performed; A-2 and A-4 showed excellent results with dose independency. [ABSTRACT FROM AUTHOR]

Abstract: A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition. [ABSTRACT FROM AUTHOR]

Background: In-vitro urease inhibitory and thermal induced protein denaturation inhibitory activities was performed for two commonly used herbal products Endemali and Akseer ULCER in the treatment of ulcers. Objectives: To evaluate the antiulcer potential of two commonly used herbal products, Endemali, Akseer ULCER. Material and Method: In urease inhibitory assay, enzyme solution, extract, diferent regaents added and absorbance was measured at 630 nm (50 min, pH 8.2) and thiourea used as standard. In protein denaturation assay, the egg albumin was mixed with different concentration of test compounds, buffer absorbance was measured. Aspirin was used as standard. Results: The Endemali had a profound effect on the urease activity in a concentration dependent manner with EC50 value of 0.468 mg/ml. The Akseer ULCER antagonized the urease activity markedly with EC50 value of 0.374 mg/ml. These tested herbal products caused marked inhibition of thermal induced protein denaturation in a concentration dependent manner. The potency in the form of EC50 for Endemali, Akseer ULCER was measured as 323, 337 μg/ml respectively. Conclusion: In short, the tested herbal drug showed strong inhibition on urease activity and inhibition on thermal induced protein denaturation thus our study validated their uses in the treatment of ulcers. [ABSTRACT FROM AUTHOR]

A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

Proteus mirabilis is a significant cause of urinary tract infection that may contribute to struvite stones. Anti-infection of this bacterium and anti-struvite formation must be considered. Sida acuta Burm. F. (SA) has been used for the treatment of diseases related to kidneys. Therefore, we investigated the effects of the SA leaf ethanolic extract (SAEE) on growth and on virulent factors (swarming motility and urease activity) of Proteusmirabilis isolated from kidney stone formers. We also evaluated anti-struvite crystal formation and phytochemical constituents of SAEE. The minimum inhibitory concentrations (MICs) of SAEE against three clinical P. mirabilis isolates were 8 mg/mL. Intriguingly, the 1/2MIC of SAEE had significant inhibitory effects on the swarming motility and urease activity of clinical P. mirabilis isolates when compared with the condition without SAEE. The SAEE at the various concentrations significantly inhibited the average weights of struvite crystals in a dose-dependent manner, compared with the control. The phytochemical analysis revealed that SAEE contained catechin, chlorogenic acid, rutin, and ferulic acid. This study indicated that SAEE has anti-P. mirabilis and anti-struvite crystal activities via its bioactive compounds. For this reason, SAEE may be developed as a new agent for the treatment of struvite stone induced by P. mirabilis. [ABSTRACT FROM AUTHOR]

Abstract: Norfloxacin was converted to 7-(4-amino-2-fluorophenyl)piperazin derivative (2) via the formation of nitro compound. The synthesis of the norfloxacin derivatives containing 1,3-thiazole or 1,3-thiazolidin moiety was performed from the reaction of 4-chlorophenacylbromide or ethyl bromoacetate with compounds 4–7 obtained starting from 2. 3-Fluoro-4-[4-(2-methoxyphenyl)piperazin-1-yl]aniline (14), 5-{[4-(2-methoxyphenyl)piperazin-1-yl]methyl}-4-phenyl-4H-1,2,4-triazole-3-thiol (18) and {[4-(2-methoxy phenyl)piperazin-1-yl]methyl}-1,3,4-oxadiazol-2-thiol (19) were obtained starting from 1-(2-methoxyphenyl)piperazine by several steps. The treatment of hydrazide (16) with several aldehydes afforded N′-[(2-hydroxyphenyl)methylen]- (20), N′-[(3-hydroxy-4-methoxy phenyl)methylen]- (21) or N′-[1H-indol-3-ylmethylene]-2-[4-(2-methoxyphenyl)piperazin-1-yl]acetohydrazide (22). Then, compounds 14, 18, 19 and 22 were condensed with 7-[4-(chloroacetyl)piperazin-1-yl]-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (3) that was obtained from norfloxacine. All newly synthesized compounds were screened for their antimicrobial activities and some of them exhibited excellent activity. Moreover, one compound was found to have antiurease activity. [Copyright &y& Elsevier]

2-[6-(Morpholin-4-yl)pyridin-3-ylamino]acetohydrazide ( 4) was obtained starting from 6-morpholin-4-ylpyridin-3-amine ( 2) via the formation of ester ( 3) and then converted to the corresponding Schiff bases ( 5, 6) with the reaction with aromatic aldehydes. The carbothioamide ( 9), obtained from the reaction of hydrazide with phenylisothiocyanate, was converted to the corresponding 1,2,4-triazole ( 11) and 1,3,4-thiadiazole ( 12) derivatives by the treatment with NaOH or HSO, respectively. The cyclocondenzation of 9 with 4-chlorophenacyl bromide or ethyl bromoacetate produced the corresponding 1,3-thiazole ( 10) or 1,3-thiazolidine derivatives ( 13), respectively. Antimicrobial and antiurease activities of newly synthesized compounds were investigated. Some of them were found to be active on M. smegmatis, and they displayed activity toward C. albicans and S. cerevisiae in high concentration. Compound 10 proved to be the most potent showing an enzyme inhibition activity with an IC = 2.37 ± 0.19 μM. [ABSTRACT FROM AUTHOR]

The objective of present study was to evaluate the antiurease and anti-oxidant activity of Vaccinium macrocarpon fruit. The parent extract was ethanolic extract while its sub fractions were prepared in n-hexane, chloroform and n-butanol. The method based on scavenging activity and reduction capability of 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH). N-butanol fraction was the most effective antioxidant with 87.0±1.15 activity but the activity was less than ascorbic acid i.e. 93.74±0.12. Highly significant urease inhibition was shown by crude ethanolic extract (71.00±0.2a) with IC50 (392.66±2.1) followed by aqueous fraction (68.00±0.5e) with IC50 (159.83±2.8). The results of crude ethanolic extract and aqueous extracts were highly significant (p<0.05) than standard Thiourea. Present study showed that Vaccinium macrocarpon exhibits potent antiurease and antioxidant activities. [ABSTRACT FROM AUTHOR]

(3β,20S,22S,25R)-22-Thiospirosol-5-en-3-ol (9) and (3β,20S,22S,25R)-22-seleno-spirosol-5-en-3-ol (11) were prepared from diosgenin (3) via 26-iodopseudodiosgenin (6) as a key intermediate. Diosgenone (15), solasodinone (16), (20S,22S,25R)-22-thio-spirosol-4-en-3-one (17), (20S,22S,25R)-22-selenospirosol-4-en-3-one (18) and (20R,22S,25R)-spirosol-4-en-3-one (19) were prepared by Oppenauer oxidation of 3, solasodine 4, 9, 11 and (3β,20R,22R,25R)-spirosol-5-en-3-ol 14, respectively. Oxidations of 15 and 16 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) provided corresponding dienone products, (20S,22S,25R)-spirosol-1,4-dien-3-one (20) and (20S,22S,25R)-22-thiospirosol-1,4-dien-3-one (21), respectively, while oxidation of 19 (C-20 diastereoisomer of 15) gave no dienone product but 21-exo vinyl product 22. 26-Thioacetylpseudodiosgenone (24) and 26-cyanoselenopseudodiosgenone (25) were prepared by treatment of 26-iodopseudodiosgenose (23), which was obtained by Oppenauer oxidation of 6, with potassium thioacetate and potassium selenocyanate, respectively. Compounds 15 and 19 exhibited more than 80% inhibitions in INF-γ productions at 10.0 μM. Compounds 4 and 25 showed cytotoxic activities (IC50=6 and 5 μM, respectively) against cancerous HCT 116 cell lines. Compounds 12 and 25 had antiurease activities (IC50=12.4 and 11.4 μM, respectively), in which only the latter showed an inhibition zone (mean zone diameter=12.2 mm) formed by Bacillus subtilis 168 trp. [ABSTRACT FROM AUTHOR]

• Antiurease activity of newly designed and synthesized thiazole-2-imine derivatives. • Docking studies were performed for all compounds and interaction modes with enzyme active sites were determined. • Machine learning method was performed to choose the most active compounds. Machine learning is one of the methods used in the design of new molecules with different biological properties and has become a trend in recent years. Since there are many published studies on urease enzyme inhibition, we accumulated a huge literatüre data set and improved a model for antiurease activity. The balanced accuracy of the selected compounds (classification models) were about 78% and the predictive accuracy of them possessed a coefficient of determination q 2 = 0.2-0.7 (regression models) with cross-validation and independent test sets. Thanks to the chemical library created with the machine learning method, a comparison of the predictive and experimental results of the compounds that previously synthesized by us and investigated urease inhibition was made. Compounds observed to be experimentally active were found to be active with the machine learning method. The models are freely avaible online (http://ochem.eu) and can be used to predict potantial antiurease activity of novel compounds. The activity potentials of compounds 4a-d were further evaluated via molecular docking studies with AutoDock4 and AutoDock Vina softwares. Urease enzyme Image, graphical abstract [ABSTRACT FROM AUTHOR]

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