Current Enzyme Inhibition - Volume 14, Issue 3, 2018

Background: With the increase of resistance rates among many pathogenic bacterial species, this led to a huge public health problem; the ongoing need for the development of new antibiotics that target new pathways is obvious. As such, the MetAP is an attractive target for the development of new antimicrobials, because it is involved in the protein processing in bacteria. Objective: To screen the potential MetAP of Mycobacterium tuberculosis inhibitor by in silico virtual screening of ZINC database and evaluate the best potential lead molecule by in vitro studies. Results and Conclusion: In this research, we used the FlexX program to screen collections of chemical compounds against the protein target. Before performing the molecular docking, FlexX was validated by tow tests to determine the reproducibility of docking program. After the virtual screening, nine chemical compounds of the top hits predicted were purchased and evaluated in vitro for their antibacterial activities against Mycobacterium smegmatis, using the paper disc diffusion method. Among the studied compounds, only the compound ZINC04785369 inhibited the bacterial growth and could be promising antimycobacterial agents. All these may provide something useful for the development of the potent inhibitors.

Background: Some of chemical syntheses are attractive because of their pharmacological application in the drug industry. Materials and Methods: In this study, water soluble peripherally and non-peripherally tetra substituted novel zinc (II) phthalocyanines, which were tagged as ZnPC, investigated against the inhibition of urease and hyaluronidase (HYA). In addition to enzyme inhibitory activities, antioxidant activity of synthesis molecules was measured by Ferric Reducing Antioxidant Power (FRAP) and DPPH radical scavenging activity assays. Results: The study also showed that four synthesis extracts exhibited a potent hyaluronidase and urease inhibitory effects with IC50 value ranges 7.095-115.878 μM and 4.227-35.678 μM respectively. Besides ZnPC-1 exhibited efficient urease and HYA inhibition, it showed good antioxidant activity with 0.341±0.001 μmol FeSO4.7H2O/mg sample for FRAP and 16.917±0.005 μM for DPPH. Also, the results obtained in the present study indicate that zinc (II) phthalocyanines compounds can be a potential source of bioactive agents.

Background: Diabetes mellitus is the most common disease in the world. One of the approaches therapy used to treat diabetes is inhibition of α -glucosidase activity by natural inhibitors from the plant. Objective: Our work comes to highlight, in vitro, the effect of phenolic extracts of some Algerian Saharan Atlas medicinal plants on the activity of α-glucosidase. Methods: The ethyl acetate extracts were prepared from hydro-methanolic (80:20) extracts of studied plants. The Folin-Ciocalteu method was used to determine the total phenolic content of the extracts. The α-glucosidase activity was determined by a microplate spectrophotometer at 405 nm using paranitrophenol α-D-glucopyranose as substrate. Results: Among the plants tested Arthrophytum scoparium, Helianthemum lippii, Equisetum arvense and Cistus villosus exhibited a strong α-glucosidase inhibitory activity. According to IC50 values, Arthrophytum scoparium exerted the highest inhibitory activity against α-glucosidase (IC50= 5.02 μM) while a weak inhibitory activity was observed with Equisetum arvense (IC50 =21.88 μM). The kinetic study revealed a noncompetitive type inhibition for Arthrophytum scoparium (KI = 4.16 μM) and Helianthemum lippii (KI = 1.46 μM) extracts whereas a full mixed type inhibition (KI = 18.17 μM; KIS = 3.98 μM) and competitive type inhibition (KI = 25 μM) were observed for Cistus villosus and Equisetum arvense, respectively. Conclusion: The results suggest that these plants represent a potential source to develop new antidiabetic drugs for controlling postprandial blood sugar.

Background: The renin-angiotensin system (RAS) is a critical contributing factor to obesity and related diseases. Several studies have shown the relationship of obesity with cyclooxygenase-2. Objectives: Based on these facts, we aimed to investigate the celecoxib oral administration (a selective anti-inflammatory inhibitor of cyclooxygenase-2 (ICOX-2)) effects, in mice fed a high-fat diet by assessing the renin-angiotensin system and inflammatory markers expression. Methods: FVB/N male mice were divided into 3 groups and fed with experimental diets, standard, high-fat diet and high-fat diet plus ICOX-2 at a dose of 100mg/kg/body weight. Body weight, food intake, blood parameters and RAS/inflammatory markers expression were assessed. Results: The main findings showed that diet-induced obese mice treated with COX-2 inhibitor showed significantly improved glucose and insulin homeostasis, presented decreased body weight gain and the biochemical analyses revealed reduced triglyceride levels and higher serum HDL-c levels as compared to HFD and ST. These results were accompanied by a downregulation of AGT, ACE, TNF-α and IL-6 expression in the group receiving treatment. Conclusion: Taken together, these results indicate that ICOX-2 may exhibit therapeutic potential for obesity via the renin-angiotensin system and inflammation.

Introduction: Sarcandra glabra has been used in traditional medicine to improve mental efficiency and to reduce stress. Volatile oil, phenolic acids, polysaccharide, terpenoids, saponins and flavonoids are bioactive compounds present in Sarcandra glabra. Materials and Methods: In this paper, we evaluated the antioxidant capacity and acetylcholinesterase (AChE) inhibitory activity in vitro of different fractions of Sarcandra glabra ethanolic extract and neuroprotective effects of EtOAc fraction of ethanolic extract on cognitive deficits mice induced with scopolamine. The leaves of Sarcandra glabra were extracted with ethanol 70% and successively fractionated with different organic solvents. These fractions were assessed the antioxidant capacity by DPPH method and AChE inhibitory activity by Ellman method. For in vivo assay, mice were administrated orally EtOAc fraction of ethanolic extract (200 mg/kg) for fourteen days, and were injected 1 mg/kg scopolamine intraperitoneally for five days to induce cognitive deficits. ACh levels and AChE activity in brain tissue were measured. Conclusion: We found that EtOAc fraction exhibited the highest of total phenolic content being equivalent to 67.4 ± 3.5 mg quercetin/g of EtOAc fraction. This EtOAc fraction also presented the strongest antioxidant activity with IC50 value of 6.84 ± 0.45 μg/mL and AChE inhibitory activity with IC50 value of 12.15 ± 1.74 μg/mL in a concentration-dependent manner. We also showed that EtOAc fraction inhibited AChE activity following mixed inhibition and Ki value of 10.54 ± 2.17 μg/mL. Scopolamine reduced the ACh levels and increased acetylcholinesterase activity in the brain tissue. Treatment with EtOAc fraction reverted the effect of SCP in the brain tissue of animals, increasing acetylcholine level and decreasing acetylcholinesterase activity. Our data demonstrated that the EtOAc fraction of Sarcandra glabra's ethanolic extract could be a benefit in the treatment of cognitive deficits.

Background: Cleome arabica belongs to the family of Capparaceae. It has attracted a great deal of attention in recent years for its pharmaceutical potentials due to its antioxidant, antihypercholisterolemic, anti-cancer and chemoprotective activities for the treatment of a number of diseases. Objective: The main study was to evaluate the α-amylase inhibitory and antioxidant activities of extracts from Cleome arabica collected on two seasons (December 2016 and May 2017) in the town of Laghouat steppe region of Algeria. In addition, the purpose of the study was to investigate a new natural inhibition of α-amylase using an in vitro model, as well as to find a natural anti-diabetic compound from the plant. Methods: The extracts were prepared with two solvent systems: hydroalcoholic and acetonic solvent systems. The polyphenolic contents of methanol and acetone extracted samples were evaluated in vitro in two different ways: total phenolic contents and total flavonoid content. The antioxidant activity was determined using 1, 1-diphenyl-2-picrylhydrazyl radical, test enzyme inhibitory effect against α-amylase of n-hexane, chloroform and ethyl acetate were investigated with spectrophotometric methods. Results: The phenolics and flavonoid contents varied from (2.87 to 107.21mg Gallic acid equivalent/ 100g dry matter) and from (0.12 to 88.50 mg Quercetin equivalent /100g) respectively for the beginning of maturity stage (December) in all plant organs. The radical scavenging activity values of the 1, 1-diphenyl-2-picrylhydrazyl radical test ranged between 0.009 to 0.481 mg/ml in different plant organ extracts. The inhibitory effect of the Cleome arabica extracts on α-amylase was also investigated and concentrations that gave 50% inhibition of maximal activity were found in acetonic extract with finest values (0.11 and 1.01 mg/ml) in the beginning and the end of maturity stage respectively at ethyl acetate and n- hexane fraction for the pods and roots, respectively. Conclusion: This study is the first report on potential inhibition of these plant extracts on the digestive enzyme, α-amylase. The results indicate that Cleome arabica of Algeria is a powerful natural antioxidant and also could provide natural biologically active agents to be used in the management of diabetes.

Introduction: This study investigated the in vitro inhibition properties of newly synthesized coumarin derivates (C1-C5) against human carbonic anhdyrase I (hCA-I) and jack bean urease. Activities were expressed as IC50 (mg/mL), the concentration reducing 50% of the enzymes. The IC50 values for hCA-I ranged 5.20 μM from 12.10 μM, with compound C3 exhibiting the highest activity. The inhibition values for urease ranged 22.30 μM to 39.00 μM, the highest activity being observed in C5. Conclusion: Comparing the inhibitions with standard inhibitors of the enzymes, while the samples exhibited moderate inhibitions against hCA I, high inhibition was determined against urease.