Synthesis and biological evaluation of new N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamides and phenylacetamides as antimicrobial agents

A new series of N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamide and phenylacetamide derivatives (1a-1n, 2a-2n) were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and their drug-resistant isolate. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 500 and 1.95 microg/ml. Benzamide derivative 1d exhibited the greatest activity with MIC values of 1.95, 3.9, and 7.8 microg/ml against drug-resistant B. subtilis, B. subtilis, and S. aureus, respectively.     

Plant growth-promoting bacteria (PGPBs) and copper (II) oxide (CuO) nanoparticle ameliorates DNA damage and DNA Methylation in wheat (Triticum aestivum L.) exposed to NaCl stress

Journal of Plant Biochemistry and Biotechnology - Wheat is the second important cereal crop worldwide due to nutritional composition and role in meeting daily energy needs. Salinity is an abiotic...     

Optimization of inoculum density to support root growth and secondary metabolite accumulation in root cultures of endangered Gentiana species: Gentiana lutea and Gentiana boissieri

In Vitro Cellular & Developmental Biology - Plant - Gentiana species belonging to the Gentianaceae family are medicinal plants rich in glycosides and phenolics. Gentiana lutea L. is a highly...     

Establishment of highly efficient and reproducible Agrobacterium-mediated transformation system for tomato (Solanum lycopersicum L.)

In Vitro Cellular & Developmental Biology - Plant - A simple and improved Agrobacterium-mediated transformation protocol of tomato (Solanum lycopersicum) cultivar Rio Grande was developed to...     

In vitro cytotoxic activity of microalgal extracts loaded nano–micro particles produced via electrospraying and microemulsion methods

Reactive oxygen species can bind protein, DNA, lipids, and carbohydrates and thus cause an oxidation reaction that induces various syndromes such as cardiovascular diseases, degenerative disease, and cancer types in the human body. Bioactive compounds, such as PUFA, EPA, DHA, and carotenoids in algae, have a chain ring and protect the tissue from chemical damage and reverse the symptoms of some diseases. Algal bioactives also have various biological properties such as anticoagulants, antiviral, antiangiogenic, antitumor, anti-inflammatory, antioxidant, antiproliferative, and immune modulation properties. This study aimed to show in vitro cytotoxic activity effect of Chlorella protothecoides and Nannochloropsis oculata microalgal extracts loaded nano–microparticles on A-172 (Homo sapiens brain glioblastoma) and HCT-116 (H. sapiens colon colorectal carcinoma) cell lines because of the increasing importance of algal biotechnology. MTT viability tests were performed on HUVEC, A172, and HCT 116 cells with particles obtained at optimum process parameters. The cell viability rates of encapsulated particles were also compared with pure algae extracts. Microalgal extracts loaded nano–micro particles showed very promising results for cytotoxic effect on cancer cells.     

Milk thistle impedes the development of carbontetrachloride-induced liver damage in rats through suppression of bcl-2 and regulating caspase pathway

Aim

The objective of this study was to examine whether MT plays a protective role against the damage in the liver by administering carbontetrachloride (CCl₄) to rats.

Main method

28 male Wistar albino (n = 28, 8 weeks old) rats have been used in the study. The rats were distributed into 4 groups according to their live weights. The groups were: (i) negative control (NC): normal water consuming group to which no CCl₄ and milk thistle (MT) is administered; (ii) positive control (PC): normal water consuming group to which no CCl₄ is administered but MT is administered; (iii) CCl₄ group: normal water consuming and group to which CCl₄ is administered (2 ml/kg live weight, ip); and (iv) CCl₄ + MT group: CCl₄ and MT administered group (2 ml/kg live weight, ip). Caspase-3, caspase-9, bax, and bcl-2 protein syntheses were examined via western blotting. MDA determination in liver tissue was made using spectrophotometer.

Key findings

MDA amount has decreased in the CCl₄ + MT group in comparison to CCl₄ group whereas caspase-3 and caspase-9 has increased and bax and bcl-2 has decreased.

Significance

These results show that MT protects the liver against oxidative damage.     

Cold-induced genetic instability in micropropagated Pistacia lentiscus L. plantlets

Genetic stability of plants during in vitro propagation and conservation is one of the important aspects of plant biotechnology. In the present study, micropropagated P. lentiscus L. shoot cultures, which are cultivated for the mastic resin, have been cold stored up to 12 months at 4 °C in the dark for different durations (2, 4, 6, 8, 10 and 12 months) and genetic alterations in cold storage conditions were evaluated. Growth parameters such as proliferation rate, shoot numbers per explant, shoot lengths and shoot forming capacity were also calculated. Since the highest proliferation rate (100 %) was obtained in 6?month-stored shoot cultures without any severe influence of cold stress on proliferation ability, amplified fragment length polymorphism (AFLP) and inter-retrotransposon amplified polymorphism (IRAP) marker systems were used to determine genetic stability in the plantlets after this storage period. Totally, 702 scorable bands were produced by 10 AFLP primer pairs. Genetic similarity value of the non-stored (control) plant and cold-stored clones ranged from 0.66 to 0.84 with a mean of 0.74. In the case of IRAP, 159 bands were produced by 8 IRAP primers. Genetic similarity value of the non-stored plant and cold-stored clones varied from 0.65 to 0.83 and the average genetic similarity value was determined as 0.72. The genetic similarity indices revealed that genetic variability was similar in both techniques. Our results showed that tissue culture and especially cold storage of P. lentiscus L. may result transposons activation, thus could cause genetic instability.     

Structure based discovery of small molecules to regulate the activity of human insulin degrading enzyme

Background

Insulin-degrading enzyme (IDE) is an allosteric Zn⁺² metalloprotease involved in the degradation of many peptides including amyloid-β, and insulin that play key roles in Alzheimer''s disease (AD) and type 2 diabetes mellitus (T2DM), respectively. Therefore, the use of therapeutic agents that regulate the activity of IDE would be a viable approach towards generating pharmaceutical treatments for these diseases. Crystal structure of IDE revealed that N-terminal has an exosite which is ∼30 Å away from the catalytic region and serves as a regulation site by orientation of the substrates of IDE to the catalytic site. It is possible to find small molecules that bind to the exosite of IDE and enhance its proteolytic activity towards different substrates.

Methodology/Principal Findings

In this study, we applied structure based drug design method combined with experimental methods to discover four novel molecules that enhance the activity of human IDE. The novel compounds, designated as D3, D4, D6, and D10 enhanced IDE mediated proteolysis of substrate V, insulin and amyloid-β, while enhanced degradation profiles were obtained towards substrate V and insulin in the presence of D10 only.

Conclusion/Significance

This paper describes the first examples of a computer-aided discovery of IDE regulators, showing that in vitro and in vivo activation of this important enzyme with small molecules is possible.     

Two different docetaxel resistant MCF-7 sublines exhibited different gene expression pattern

The objective of the present study was to investigate gene expression pattern of two docetaxel resistant MCF-7 breast carcinoma sublines step wisely selected in 30 and 120 nM docetaxel. Cell proliferation assay was performed in order to demonstrate development of docetaxel resistance. cDNA microarray analysis was performed using Affymetrix^® Human Genome U133 Plus 2.0 Arrays in duplicate experiments. Quantitative and semi-quantitative gene expression analysis was also performed to confirm gene expression analysis for selected genes. XTT results demonstrated that 30 (MCF-7/30nM DOC) and 120 nM (MCF-7/120nM DOC) docetaxel selected cells were 13- and 47-fold resistant, respectively. cDNA microarray analysis demonstrated that expression profiles of MCF-7 and MCF-7/30nM DOC were more similar to each other where expression profile of MCF-7/120nM DOC was different as examined by line graphs and scatter plots. 2,837 and 4,036 genes were significantly altered in 30 and 120 nM docetaxel resistant sublines, respectively. Among these, 849 genes were altered in common in two docetaxel resistant sublines. Antiapoptotic gene expression (e.g., Bcl-2 and APRIL) were noticeably altered in MCF-7/30nM DOC. However, docetaxel resistance in MCF-7/120nM DOC were more complicated with the involvement of ECM related gene expression, cytokine and growth factor signaling, ROS metabolism and EMT related gene expression together with higher level of MDR1 expression. Expression profiles in 30 and 120 nM docetaxel resistant sublines changed gradually with increasing resistance index. Drug resistance development seems to be step wise event in MCF-7 cells.