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Herein, we have synthesized a series of novel fifteen 2-aryl benzimidazole derivatives 8a–o and tested their bioactivity as potent urease inhibitors. The structures of the 8a–o were elucidated using spectroscopic technics (1H-NMR, 13C-NMR, MS), elemental analysis, and melting point. The urease inhibition activity was evaluated using the urease enzyme inhibition kit. All 8a–o showed higher urease inhibition activity (7.74 to 21.18 µM) in comparison to thiourea and hydroxyurea as standard (IC50: 22 and 100 µM respectively). 8m, 8n, and 8o exhibited the best activity with the IC50 value of 7.74, 8.09, and 8.56 µM respectively. Docking study represented the possible mode of interactions between the most active compound and the residues of the enzyme's active site. To investigate the cytotoxicity profile of the target compounds, the MTT assay was performed on two different cell lines. The results showed that all 8a–o derivatives display IC50 values higher than 50 µM toward both tested cell lines. [ABSTRACT FROM AUTHOR]

Cancer pain management is mostly done by opioids; however, they have further pharmacological effects apart from analgesia including angiogenesis. In this study, peripherally acting ligands of µ opioid receptor (MOR) were synthesized and evaluated as a tool to investigate peripheral effects of opioids in controlling angiogenesis. For this purpose, the designed compounds were synthesized from thebaine and N-(4-dimethylaminophenyl)maleimide under Diels-Alder and nucleophilic substitution (SN) reactions with different alkyl halides to form quaternary ammonium salts. In silico study conducted by docking these compounds on active (5C1M) and inactive (4DKL) form of MOR. Results of in silico study indicate that all compounds were more likely to be an antagonist of MOR based on their interaction patterns with MOR. For biological assessment, they were tested on human umbilical vein endothelial cells using a proliferation MTT test. Also, these compounds were studied by in vivo hot plate test to examine the ability of compounds to cross the blood-brain barrier (BBB). In biological tests, these compounds showed double-faced results with pro-angiogenic effect in lower doses and anti-angiogenic effect in higher doses. Their pro-angiogenic effect was comparable with VEGF. The in vivo study proved their peripherally acting nature. The contradictory effects of opioids on angiogenesis could be explained by its two different targets including MOR and opioid growth factor receptor. This gives a privilege to opioids for use as an angiogenesis controller. By developing more peripherally acting opioids with minimizing central effects, more research in this area is hoped. [ABSTRACT FROM AUTHOR]

In this work, a novel series of phthalimide-4,5-dihydrothiazole-amide derivatives 5a–f have been synthesized and evaluated for their anti-epileptic activities against pentylenetetrazole (PTZ)-induced seizure in mice. Among the synthesized compounds, the most potent was 4-chloro derivative 5b with zero mortality in PTZ test. Molecular docking was performed to investigate the modes of interactions between GABAA receptor and synthetized compounds. Docking results were in good agreement with observed experimental data and indicate that among six new derivatives, compound 5b with highest effective anticonvulsant properties, had lowest binding energy. This compound also exhibited better anti-epileptic activity and lower binding energy for connect to GABAA receptor in comparison to thalidomide as standard anti-epileptic agent. [ABSTRACT FROM AUTHOR]

A series of benzimidazole derivatives 8a–h were synthesized in acceptable yield and characterized by spectroscopic methods such as 1H-NMR, 13C-NMR, MS, and Elemental analysis. In the urease inhibitory assay, all 8a–h showed higher urease inhibition activity (IC50: 5.85–20.82 µM) in comparison to thiourea and hydroxyurea as standard (IC50: 22 and 100 µM respectively). 8g exhibited the best activity with the IC50 value of 5.85 µM. The docking study represented a possible mode of interaction between 8g and the active site. To investigate the cytotoxicity of the synthesized compounds, an MTT assay was performed on two different cell lines which showed 8a–h have IC50 values higher than 50 µM on both tested cell lines. 8a–h were checked for antibacterial activity and the best activity was found by 8d against Helicobacter pylori with an inhibition zone of 20 mm even stronger than gentamicin with an inhibition zone of 18 mm. [ABSTRACT FROM AUTHOR]

Herein, we synthesized a series of novel benzimidazole derivatives 5a–k and screened their bioactivity as potent urease inhibitors. The structure of the 5a–k was elucidated using spectroscopic technics (1H-NMR, 13C-NMR, MS), elemental analysis, and melting point. The urease inhibition activity was evaluated using the urease enzyme inhibition kit. All 5a–k, except 5d, showed higher urease inhibition activity (0.77 to 6.25 µM) in comparison to thiourea and hydroxyurea as standard (IC50: 22 and 100 µM respectively). 5c and 5j exhibited the best activity with the IC50 value of 0.77 and 1.26 µM respectively. A molecular docking study showed the mode of interactions between the most active compound and enzyme active site. To investigate the cytotoxicity profile of the target compounds, an MTT assay was done on two different cell lines which showed all 5a–k have IC50 values higher than 50 µM on both tested cell lines. [ABSTRACT FROM AUTHOR]

The signaling lymphocytic activation molecule F7 (CS-1) enables the selective killing of the myeloma cells with minimal side effects on the healthy tissue. In this study, we have modelled the 3D structure of CS-1 followed by performing molecular dynamic simulations. To develop a potential CS-1 modulator, a virtual screening of the 'Bioactive Compound Database' was conducted. The screening results have given three interacting regions. The best representative structure of each class and mode of action were revealed. Our study suggests compounds ICG-001, Avanafil, and BPTES, as novel drug candidates at the CS-1 protein target. The molecular dynamic simulation study reveals that the resulted compounds provide different binding patterns over the CS-1 Ig-like V-type domain in which Avanafil and BPTES provide stable interactions with their binding environment located at the bc-hi loops clefts and bc-fg loops clefts, respectively. In contrast, compound ICG-001 shows more flexible and transient non-binding interaction due to the vast binding region over β-sheet strands consisting of H, C and D during the simulation timeline. We conclude that the identified compounds seem to be the best candidates to design a series of new compounds with the ability to bind to CS-1 with potential binding activity to its target. [ABSTRACT FROM AUTHOR]

In this paper, a new series of isatin-sulphonamide based derivatives were designed, synthesised and evaluated as caspase inhibitors. The compounds containing 1-(pyrrolidinyl)sulphonyl and 2-(phenoxymethyl)pyrrolidin-1-yl)sulphonyl substitution at C5 position of isatin core exhibited better results compared to unsubstituted derivatives. According to the results of caspase inhibitory activity, compound 20d showed moderate inhibitory activity against caspase-3 and −7 in vitro compared to Ac-DEVD-CHO (IC50 = 0.016 ± 0.002 μM). Among the studied compounds, some active inhibitors with IC50s in the range of 2.33–116.91 μM were identified. The activity of compound 20d was rationalised by the molecular modelling studies exhibiting the additional van der Waals interaction of N-phenylacetamide substitution along with efficacious T-shaped π-π and pi-cation interactions. The introduction of compound 20d with good caspase inhibitory activity will help researchers to find more potent agents. [ABSTRACT FROM AUTHOR]

Currently, the demand for biodegradable packaging as one of the preferable preservation technologies to prevent food spoilage is increasing. The aim of this study was to evaluate a new eco-friendly coating with free and nano-encapsulated Cuminum Cyminum L. aqueous extract (CCE) on quality attributes of sardine fish. The microstructural changes were evaluated after the addition of extract (E), nanoextract (NE), and nanoliposome by measuring the mean size of nonoliposomes, zeta potential, scanning electron microscopy (SEM), as well as Fourier-transform infrared spectroscopy (FTIR). The use of cumin remarkably (p <.05) reduced the peroxide value (PV), total volatile basic nitrogen (TVB-N), pH, and thiobarbituric acid (TBA). Cumin extract coatings especially in the form of nanoliposome showed inhibitory effect on the total viable counts (TVC) and lactic acid bacteria (LAB). Moreover, nano-encapsulation of CCE provided a controlled release of this compound on the sardine surface, which prolonged the antioxidant activity of coating during storage compared with other groups (nano chitosan, nanochitosan-E, and control groups). As a result, nano chitosan (NCh) coating with CCE-encapsulated nanoliposomes can be used as effective active packaging. [ABSTRACT FROM AUTHOR]

A simple and sensitive extractive spectrophotometric method has been described for the determination of Ketotifen. The developed method is based on the formation of a colored ion-pair complex (1:1 drug/dye) of Ketotifen and bromocresol green in buffer pH 3 and extraction in chloroform. The extracted complex shows absorbance maxima at 423 nm. Beer's law is obeyed in the concentration range of 5.15-61.91 µg/ml. The proposed method has been applied successfully for the determination of drug in commercial tablets and syrup dosage form. No significant interference was observed from the excipients commonly used as pharmaceutical aids with the assay procedure. [ABSTRACT FROM AUTHOR]