Current Chemical Biology - Volume 14, Issue 3, 2020

Heat shock proteins (Hsps) are a group of proteins that serve to improve cell survival in response to a variety of environmental stresses of the host. In recent years, Hsps gained interest in cancer therapy and as drug target against microbial infections. The antimicrobial resistance especially by Gram-negative pathogens poses a threat to mankind. The pathogen proteins of Hsp family yield Hsp90 inhibitor antibiotic reveal mechanisms that interact with the ADP/ATP-sites of Hsp90. For the present review, we used the databases and websites PubMed, SciFinder, Scopus, ProQuest, Google and Google Scholar. The review discusses the development of Hsp90 inhibitors for bacterial as well as fungal infections and how these inhibitors are being used for clinical trials. A systematic web search analysis was conducted from April to November 2019.

Background: Wound healing is a complex process necessary for repairing damaged tissues and preventing infection. Selenium nanoparticles (Se NPs) were known due to their antioxidant and antimicrobial effects, also niacin has angiogenesis and antioxidant effects that are important in wound healing. Objective: The present study was conducted to investigate the effect of Se NPs and niacin in reducing and accelerating the wound healing time in mice. Methods: A simple wet chemical method has been modified to synthesize Se NPs in order to investigate their effect and niacin on reducing the wound healing in 80 adult female albino mice (250 mm² full thickness open excision wound) that were divided into eight groups (10 mice/each). After 30-days, the mice were sacrificed, blood and tissue samples were taken for analysis. Results: The results showed that the percentage of wound area had been significantly reduced in Se NPs and niacin treated groups compared to the positive control. The level of Vascular Endothelial cell Growth Factor and Collagenase I in Se NPs and niacin groups significantly exceed those of other groups while Nitric Oxide (NO) was significantly decreased in treated groups. Liver and kidney functions showed the lower toxicity effect of Se NPs and niacin. Skin tissue showed the wound healing effect of Se NPs and niacin by regenerating skin layer compared to the positive group. Discussion: The high antioxidant property and low hemolysis activity of Se NPs and niacin proved the biocompatible nature of Se NPs and niacin. A possible mechanism depending on the obtained results has been proposed. Conclusion: Se NPs and niacin play an important role in accelerating and reducing the time of wound healing while they were antagonistic to each other.

Background: The Eucalyptus globulus extractions have been used by the traditional healers to treat diseases in the study area. Our previous study revealed that the essential oil has antimicrobial and antifungal activity. This study determined phytochemical analysis, skin irritation, acute and subacute toxicity of Eucalyptus globulus essential oil in mice and rats. Methods: The phytochemicals were analyzed using GC-MS mass spectrometry. The acute toxicity study was determined at three dose levels of 1500 mg/kg, 1750mg/kg, and 2000 mg/kg. The essential oil limit test at a dose of 1000 mg/kg was administered to mice for 28 consecutive days for sub-acute toxicity study. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were analyzed for histopathological analyses. The 5% ointment formulation was applied to the rat skin to determine skin irritation effects. Results: The Eucalyptus globulus essential oil showed no effect on the mice at a dose of 1500mg/kg and below, but caused signs of toxicity and death at a dose of 1750mg/kg and above compared to the controls (p<0.05). The LD50 value was 1650 mg/kg. There was no significant difference (p>0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control at 1000 mg/kg subacute toxicity study. No histopathological changes were detected in the organs tested. The 5% ointment formulation did not show any abnormal skin reaction. Discussion: In the present study, the Eucalyptus globulus essential oil was comparable with other studies in terms of both chemical composition and its effects on sub-acute and topical application. Conclusion: This toxicity study demonstrated that Eucalyptus globulus essential oil is nontoxic at a relatively lower concentration.

Background: A snake bite is fundamentally an injury often resulting in puncture wounds meted out by the animal's fangs and occasionally resulting in envenomation. Rate of snake bites around 5,400,000 bites per year leads to over 2,500,000 envenomings and around 125,000 fatal cases annually. Snake venom enzymes are rich in metalloproteinases, phospholipaseA2, proteinases, acetylcholinesterases and hyaluronidases. Objective: Cyphostemma adenocoule is traditionally being used for the treatment of snake bites in Eritrea. The present research was aimed at evaluating the snake venom enzyme inhibition activity of C. adenocoule against puff adder venom and developing a base for the traditional use of the plant against snakebites in Eritrea. Methods: The anti-venom activity of C. adenocoule was assessed in-vitro through phospholipaseA2 enzyme inhibition assay using egg yolk as a cell. The ethanol and chloroform extracts of C. adenocoule showed in vitro anti phospholipase A2 activity, whereas the water extracts of the plant showed no activity. Results: Among the extracts of C. adenocoule, the highest percentage of inhibition was obtained from chloroform extract (95.55% at 100mg/ml). The extract showed prominent activity at different concentrations (34.7% at10mg/ml, 48.8% at 20mg/ml, 54.8% at 40mg/ml, 60.9% at 60mg/ml, 80.5% at 80mg /ml). The ethanol extract also showed certain activity at various concentrations (25.22% at10mg/ml, 14.78% at 20mg/ml, 2.6% at40mg/ml). The activity of the chloroform extracts increases as concentration increases, whereas the activity of the ethanol extracts decreases as concentration increases. The aqueous extract of C. adenocoule did not show any activity at all concentrations. Conclusion: In this study, the chloroform and ethanol extracts of the plant inhibited the enzyme of interest and thus proved the efficacy of anti-snake venom activity of the plant.

Background: The binding of free iron ions in the composition of nitrosyl complexes is probably one of the mechanisms of the antioxidant action of nitric oxide. The study of the protective properties of nitric oxide is often carried out using exogenous NO donors. In our work, we used nitric oxide donor - sodium μ2-dithiosulfate-tetranitosyldiferrate tetrahydrate (TNIC-thio). Objective: The aim of our work was to investigate the possibility of using TNIC-thio to increase the resistance of plants to stress factors. Since the implementation of anti-stress programs requires a lot of energy expenditure, we studied the functional state of the mitochondria of pea seedlings under conditions of water deficiency and treatment with TNIC-thio. Materials and Methods: The functional state of the mitochondria was studied as per the level of lipid peroxidation by the spectrofluorimetry, by a fatty acid composition of mitochondrial membranes with the chromatography technique and by the morphology of mitochondria with the atomic force microscopy. Results: Water deficiency has caused changes in the Fatty Acid (FA) composition, which manifested themselves in increasing the content of saturated FAs and decreasing the content of unsaturated FAs containing 18 and 20 carbon atoms. Treatment of pea seeds with 10-8 M TNIC-thio under these conditions led to the prevention of LPO, prevention of changes in the FA composition of mitochondrial membranes and reduction in the number of swollen organelles. Conclusion: It can be assumed that the protective effect of TNIC-thio is due to the preservation of the functional state of the mitochondria.

Background: Aggregation of misfolded proteins under stress conditions in the cell might lead to several neurodegenerative disorders. Amyloid-beta (Aβ1-42) peptide, the causative agent of Alzheimer’s disease, has the propensity to fold into β-sheets under stress, forming aggregated amyloid plaques. This is influenced by factors such as pH, temperature, metal ions, mutation of residues, and ionic strength of the solution. There are several studies that have highlighted the importance of ionic strength in affecting the folding and aggregation propensity of Aβ1-42 peptide. Objective: To understand the effect of ionic strength of the solution on the aggregation propensity of Aβ1-42 peptide, using computational approaches. Materials and Methods: In this study, Molecular Dynamics (MD) simulations were performed on Aβ1-42 peptide monomer placed in (i) 0 M, (ii) 0.15 M, and (iii) 0.30 M concentration of NaCl solution. To prepare the input files for the MD simulations, we have used the Amberff99SB force field. The conformational dynamics of Aβ1-42 peptide monomer in different ionic strengths of the solutions were illustrated from the analysis of the corresponding MD trajectory using the CPPtraj tool. Results: From the MD trajectory analysis, we observe that with an increase in the ionic strength of the solution, Aβ1-42 peptide monomer shows a lesser tendency to undergo aggregation. From RMSD and SASA analysis, we noticed that Aβ1-42 peptide monomer undergoes a rapid change in conformation with an increase in the ionic strength of the solution. In addition, from the radius of gyration (Rg) analysis, we observed Aβ1-42 peptide monomer to be more compact at moderate ionic strength of the solution. Aβ1-42 peptide was also found to hold its helical secondary structure at moderate and higher ionic strengths of the solution. The diffusion coefficient of Aβ1-42 peptide monomer was also found to vary with the ionic strength of the solution. We observed a relatively higher diffusion coefficient value for Aβ1-42 peptide at moderate ionic strength of the solution. Conclusion: Our findings from this computational study highlight the marked effect of ionic strength of the solution on the conformational dynamics and aggregation propensity of Aβ1-42 peptide monomer.