Benzimidazolone-piperazine/triazole/thiadiazole/furan/thiophene conjugates: Synthesis, in vitro urease inhibition, and in silico molecular docking studies.

This study describes the synthesis, in vitro urease inhibition, and molecular docking studies of benzimidazolone derivatives incorporating the piperazine, triazole, thiadiazole, furan, thiophene, and thiosemicarbazide moieties. All newly synthesized compounds demonstrated varying degrees of urease inhibitory activity, with IC50 values ranging between 0.64 ± 0.099 and 0.11 ± 0.017 µM, when compared with the standard drug thiourea (IC50 value of 0.51 ± 0.028 µM). To confirm the experimental urease inhibition results and elucidate the mode of interaction of the synthesized compounds with the binding site of the urease enzyme, molecular docking studies were performed using the Schrödinger Suite package. Molecular docking studies showed that compounds with high in vitro urease inhibition interacted with key residues of the urease active site such as His221, Glu222, Asp223, His322, Arg338, and Ni2+ cations via hydrogen bonding, metal coordination, salt bridge, π-π stacking, and π-cation interactions.

Design, molecular docking and synthesis of novel 5,6-dichloro-2-methyl-1H-benzimidazole derivatives as potential urease enzyme inhibitors.

A novel series of 5,6-dichloro-2-methyl-1H-benzimidazole derivatives was synthesized and then screened for their urease inhibitory activity. All compounds showed more potent inhibitory activity in the range of IC50 = 0.0294 ±â€¯0.0015-0.1494 ±â€¯0.0041 µM than thiourea (IC50 = 0.5117 ±â€¯0.0159 µM), as a reference inhibitor. Among all the tested compounds, the compound 15 (IC50 = 0.0294 ±â€¯0.0015 µM) having strong electron-withdrawing nitro group on the phenyl ring was recorded as the most potent inhibitor of urease. All compounds were docked at the active sites of the Jack bean urease enzyme to investigate the reason of the inhibitory activity and the possible binding interactions of enzyme-ligand complexes.

Synthesis and molecular docking study of some 5,6-dichloro-2-cyclopropyl-1H-benzimidazole derivatives bearing triazole, oxadiazole, and imine functionalities as potent inhibitors of urease.

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-1H-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 IC50=0.06µM. Molecular docking studies were also conducted on enzyme extracted from Jack bean urease to identify the binding mode of the newly synthesized compounds.

Synthesis, antibacterial, antielastase, antiurease and antioxidant activities of new 1,4-butylene bridged bis-1,2,4-triazole derivatives.

A new bis schiffbases, 3 a-b were synthesized compound 2 with various bis aldehydes. Compounds 3 a-b have been reduced with NaBH(4) to afford the corresponding bis amino triazole compounds 4 a-b. The obtained products 3 a-b and 4 a-b were identified by FTIR, (1)H-NMR, (13)C-NMR. A series of triazol derivatives were evaluated for their antibacterial, antioxidant, antiurease and antielastase activities. The results showed that the synthesized new bis-1,2,4-triazole derivatives had effective antioxidant, antiurease and antielastase activities.

Synthesis, antibacterial, antielastase, antiurease and antioxidant activities of new methoxy substitued bis-1,2,4-triazole derivatives.

The methoxy substitued two novel bis triazole-schiff bases (6 a-b) were synthesized with 4-amino-3,5-diethyl-4H-1,2,4-triazole and various bis-aldehydes. Their amine derivatives prepared by reduced with NaBH(4) (5 a-b). The obtained products 6 a-b and 7 a-b were identified by FT-IR, (1)H-NMR, (13)C-NMR. The bis triazole-schiff bases and amine derivatives were tested for antimicrobial activity using the agar diffusion technique against 11 bacteria. The synthesized compounds (6 a-b and 7 a-b) were screened for their antielastase, antiurease and antioxidant activities. The resuts showed that the synthesized compounds (6 a-b and 7 a-b) had effective antielastase and antiurease activities.

Synthesis, antielastase, antioxidant and radical scavenging activities of 4-(aza substituted) methylene substituted dihydroxy coumarines.

A series of some 4-(aza substituted) methylene substituted dihydroxy coumarines were evaluated for their antioxidant and antielastase activities. Different in vitro methodologies such as total reducing power, 1,1-diphenyl-2-picryl-hydrazil (DPPH·) free radical scavenging, ABTS radical scavenging activity were used as antioxidant activity. All the tested compounds exhibited potent free radical scavenging ability and antielastase activites.

Antimicrobial and antiurease activities of newly synthesized morpholine derivatives containing an azole nucleus.

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 H2SO4, 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 IC50 = 2.37 ± 0.19 µM.

Synthesis and spectroscopic characterization of novel methoxy bridged benzimidazolyl-substituted phthalocyanines as potent inhibitors of urease.

In this study, novel peripherally 4-[(1H-benzimidazol-1-yl)methoxy] substituted Zn(II) (3) Cu(II) (4) and Co(II) (5) phthalocyanines were prepared and their structures were characterized spectroscopically. The light absorption behaviors of the synthesized compounds (3-5) were studied by UV-Vis spectroscopy at different concentrations in different solvents. The urease inhibition activities of the synthesized compounds were also investigated. Among the synthesized molecules, compound 4 showed the best inhibitory effect against jack bean urease with IC50 values of 0.0036 ±â€¯0.0010 µM.

Synthesis, antibacterial, antiurease, and antioxidant activities of some new 1,2,4-triazole schiff base and amine derivatives.

The acylhydrazone compound named ethyl N'-furan-2-carbonylbenzohydrazonate was synthesized by the condensation of ethyl benzimidate hydrochloride with furan-2-carbohydrazide. The treatment of the acylhydrazone with hydrazine hydrate afforded 4-amino-3-furan-2-yl-5-phenyl-1,2,4-triazole. The usage of this compound with various aromatic aldehydes resulted in the formation of 4-arylidenamino-3-furan-2-yl-5-phenyl-1,2,4-triazoles. Sodium borohydride reduction of 4-arylidenamino derivatives afforded 4-alkylamino-3-furan-2-yl-5-phenyl-1,2,4-triazoles. The obtained products were identified by FT-IR, (1)H-NMR, (13)C-NMR. A series of compounds were evaluated for their antibacterial, antiurease, and antioxidant activities. The results showed that the synthesized new compounds had effective antiurease and antioxidant activities.

Some monohydroxy tetradecanoic acid isomers as novel urease and elastase inhibitors and as new antioxidants.

A series of some 3-,6-,7-,9-,12- monohydroxy tetradecanoic acids were evaluated for their antiurease, antielastase and antioxidant activities for the first time in this study. All the test compounds exhibited antioxidant, antielastase and antiurease activities. The relationship between the position of the hydroxy group and the enzyme inhibition effect is studied in this work. The mentioned biological activities are depending on the position of hydroxy group of tetradecanoic acid isomers. The results obtained in this work are indicating that 3-,6-,7-,9-,12-monohydroxy tetradecanoic acid isomers can be used in agriculture, pharmacy and cosmetic industries due to their excellent antielastase, antiurease and antioxidant activities.

Antibacterial, antiurease, and antioxidant activities of some arylidene barbiturates.

Some series of arylidene barbiturates and thiobarbiturates were evaluated for their antibacterial, antioxidant, and urease inhibition activities. The arylidene barbiturates and thiobarbiturates were tested for antimicrobial activity using the agar well diffusion technique against 13 bacteria. The synthesized compounds (1a-g) were screened for antiurease and antioxidant activities. The results showed that the synthesized compounds (1a-g) had effective antiurease, antioxidant, and antibacterial activities.

Effects of vitamin U (S-methyl methionine sulphonium chloride) on valproic acid induced liver injury in rats.

In this study, we aimed to investigate the effects of vitamin U (Vit U) on valproic acid (VPA)-induced liver damage. Female Sprague Dawley rats were randomly divided into four groups. Group I was intact control animals. Group II was control rats given Vit U (50 mg/kg/day) for fifteen days. Group III was given only VPA (500 mg/kg/day) for fifteen days. Group IV was given VPA+Vit U (in same dose and time). Vit U was given to rats by gavage and VPA was given intraperitoneally. On the 16th day of experiment, all the animals were fasted overnight and then sacrificed under ether anesthesia. Liver tissue was taken from animals, homogenized in 0.9% saline to make up to 10% homogenate. Liver aspartate and alanine transaminases, alkaline phosphatase, lactate dehydrogenase, myeloperoxidase, sorbitol dehydrogenase, glutamate dehydrogenase and xanthine oxidase activities and lipid peroxidation levels were increased and paraoxonase activity and glutathione levels were decreased in VPA group. Treatment with Vit U reversed these effects. These results demonstrated that administration of Vit U is a potentially beneficial agent to reduce the liver damage in VPA induced hepatotoxicity, probably by decreasing oxidative stress.