Degree Of Growth Inhibition Research Articles

The Discovery of Cyclic Lipopeptide Olenamidonins in a Deepsea-Derived Streptomyces Strain by Knocking Out a DtxR Family Regulator.

Three new cyclic lipopeptides, olenamidonins A-C (1-3), in addition to two previously reported metabolites (4 and 5), were accumulated in the ΔdtxRso deletion mutant of deepsea-derived Streptomyces olivaceus SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds 1-5 displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains Enterococcus faecalis CCARM 5172 and Enterococcus faecium CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 μg/mL.

Anti-staphylococcal activity of soilless cultivated cannabis across the whole vegetation cycle under various nutritional treatments in relation to cannabinoid content

Antibiotic resistance in staphylococcal strains and its impact on public health and agriculture are global problems. The development of new anti-staphylococcal agents is an effective strategy for addressing the increasing incidence of bacterial resistance. In this study, ethanolic extracts of Cannabis sativa L. made from plant parts harvested during the whole vegetation cycle under various nutritional treatments were assessed for in vitro anti-staphylococcal effects. The results showed that all the cannabis extracts tested exhibited a certain degree of growth inhibition against bacterial strains of Staphylococcus aureus, including antibiotic-resistant and antibiotic-sensitive forms. The highest antibacterial activity of the extracts was observed from the 5th to the 13th week of plant growth across all the nutritional treatments tested, with minimum inhibitory concentrations ranging from 32 to 64 µg/mL. Using HPLC, Δ9-tetrahydrocannabinolic acid (THCA) was identified as the most abundant cannabinoid in the ethanolic extracts. A homolog of THCA, tetrahydrocannabivarinic acid (THCVA), reduced bacterial growth by 74%. These findings suggest that the cannabis extracts tested in this study can be used for the development of new anti-staphylococcal compounds with improved efficacy.

Multifaceted effects of volatile organic compounds released by Fusarium oxysporum on Trichoderma biocontrol agents

We investigated how volatile organic compounds (VOCs) produced by Fusarium oxysporum, a soilborne fungal species complex that infects diverse plants, affect the growth of four Trichoderma spp. and their secretion of antifungal molecules and gene expression to evaluate the involvement of VOC-mediated recognition of pathogens in biocontrol. Five VOCs commonly produced by all F. oxysporum strains analyzed, including 4-ethylanisole, 1-hexanol, 3-methyl-1-butanol, isopentyl acetate, and 2-phenylethanol, were tested. All compounds inhibited Trichoderma growth in a concentration-dependent manner, with 4-ethylanisole being the most effective. Although the degree of growth inhibition by each compound was similar among the four species, their secretion of antifungal molecules varied widely, with the degree of induction in T. virens and T. viride being higher than that in T. harzianum and T. asperellum in most treatments. Transcriptome analyses via RNA-seq after exposure to 4-ethylasniole, 3-methyl-1-butanol, isopentyl acetate, and VOCs released by three F. oxysporum strains were performed. Analysis of gene ontology (GO) terms enriched among the differentially expressed genes (DEGs) revealed that diverse processes, such as synthesizing/metabolizing various types of organic compounds, ion/carbohydrate transport, proteolysis, response to stimulus, signal transduction, chromosome organization, RNA processing, and DNA metabolism, were significantly affected. Some genes likely involved in biocontrol, such as those that perform fungal cell wall degradation, protein hydrolysis, and secondary metabolite biosynthesis, were also differentially regulated. However, the DEGs in the four species did not overlap significantly, suggesting that individual species respond distinctly to each VOC treatment. Collectively, our data suggest that Trichoderma BCAs recognize other fungi through multiple specific volatile cues and prepare for subsequent encounters. We discuss future studies needed to test this hypothesis and to uncover the mechanism underlying the VOC-mediated recognition of pathogens and the resulting modulation of diverse cellular responses.

The Inhibitory Activity of Lactobacillus plantarum Supernatant against Enterobacteria, Campylobacter, and Tumor Cells.

Cell-free supernatant of Lactobacillus plantarum exhibit a strong antimicrobial effect against a number of pathogenic enterobacteria (E. coli, Shigella flexneri, Salmonella typhimurium, Proteus mirabilis, and Campylobacter jejuni). The degree of growth inhibition in broth culture reached a high level for all tested bacteria. The highest rates were noted for P. mirabilis (by 13 times) and the lowest for S. flexneri (by 5 times) and C. jejuni (by 4.5 times). Significant antiproliferative effect of the supernatant on cells of tumor-derived epithelial cell lines was shown. The highest degree of inhibition (by 22 times) was observed for HT-29 cells (colon carcinoma). Thus, inclusion of probiotics in traditional treatment schemes can increase the effectiveness of antibacterial and antitumor drug therapy.

Isolation and characterization of phosphate-solubilizing bacteria from rhizosphere of poplar on road verge and their antagonistic potential against various phytopathogens

BackgroundPhosphate-solubilizing bacteria (PSB) can solubilize insoluble phosphate compounds and improve phosphate availability in soil. Road verges are important in urban landscaping, but the population structure of PSB and their ecological functions in the road verge soil is still unclear.ResultsTwenty-one mineral PSB strains and 14 organic PSB strains were isolated from the rhizosphere of poplar on urban road verge. All the mineral PSB strains showed better solubilization to Ca3(PO4)2 than FePO4 or AlPO4. Among them, 7 strains showed high phosphate-solubilizing (PS) activities to Ca3(PO4)2 (150–453 mg/L). All the organic PSB strains displayed weak solubilization to lecithin. 16S rRNA gene-based phylogenetic analysis showed good species diversity of the PSB strains, which belongs to 12 genera: Bacillus, Cedecea, Cellulosimicrobium, Delftia, Ensifer, Paenibacillus, Pantoea, Phyllobacterium, Pseudomonas, Rhizobium, Sinorhizobium and Staphylococcus. Moreover, 8 PSB strains showed various degrees of growth inhibition against 4 plant pathogenic fungi, Fusarium oxysporum S1, F. oxysporum S2, Pythium deliense Meurs Z4, Phomopsis sp. AC1 and a plant pathogenic bacterium, Pectobacterium carotovorum TP1.ConclusionsThe results indicated that these PSB strains could perform multiple ecological functions on road verge. The development and application of bio-agents based on the strains would provide a new strategy for maintaining and improving the ecosystem stability of road verges.

Cu2O Nanoparticles Deposited on Y2O3 and CuO: Synthesis and Antimicrobial Properties

This paper reports the preparation of copper(I) oxide nanoparticles deposited on yttrium oxide and copper(II) oxide in the presence of acerola and white willow extracts. Through the use of natural compounds, it was possible to modify the surface of the Y2O3 and CuO carriers allowing Cu2O to be deposited to a greater extent, thus improving the antibacterial properties of the materials. Cu2O nanoparticles, by being deposited on a carrier, enable an increase in the contact surface of the nanoparticles with microorganisms, which react to form reactive oxygen species. Cu2O nanoparticles with sizes of about 38 nm and 76 nm were obtained for Y2O3- and CuO-deposited nanoparticles, respectively. The Gram-negative bacteria Escherichia coli shown a greater sensitivity to the degree of inhibition compared to Staphylococcus Aureus already at a concentration of 250 mg/L. For almost all materials, the inhibition level remained above 50% after 48 h. Analysis of the effect of the antimicrobial properties of the materials against Candida albicans fungus shown high activity which was obtained only at the highest concentrations of 8000 mg/L, for which the degree of growth inhibition was 100% also after 48 h for both Y2O3–Cu2O and CuO–Cu2O.

Toxic effects of microplastics in plants depend more by their surface functional groups than just accumulation contents

Differentially charged microplastics (MPs) engendered by plastic aging (e.g., plastic film) widely existed in the agricultural ecosystem, yet minimal was known about the toxic effects of MPs on plants and their absorption and accumulation characteristics. Root absorption largely determined the migration and accumulation risks of MPs in the soil-crop food chain. Here, five types of MPs exposure experiments of leaf lettuce were implemented to simulate root absorption by hydroponics. MPs exposure caused different degrees of growth inhibition, root lignification, root cell apoptosis, and oxidative stress responses; accelerated chlorophyll decomposition and hampered normal electron transfer within the PSII photosystem. Moreover, the uptake of essential elements by roots was inhibited to varying degrees due to the pore blockage in the cell wall and the hetero-aggregation of opposite charges after MPs exposure. MPs exposure observably up-regulated the organic metabolic pathways in roots, thus affecting MPs mobility and absorption through the electrostatic and hydrophobic interactions between the root exudations and MPs. Importantly, MPs penetrated the root extracellular cortex into the stele and were transported to the shoots by transpiration through xylem vessels based on confocal laser scanning microscopy and scanning electron microscopy images. Quantitative analysis of MPs indicated that their toxic effects on plants were determined to a greater extent by the types of surface functional groups than just their accumulation contents, that is, MPs were confirmed edible risks through crop food chain transfer, but bioaccumulation varied by surface functional groups.

A maize gene coding for a chimeric superlectin reduces growth of maize fungal pathogens and insect pests when expressed transgenically in maize callus

Plant breeding for pest resistance is a long process, and the rate of development of resistant varieties would be accelerated if resistance genes to multiple pests could be identified. A gene located in a resistance locus was cloned from a maize inbred with resistance to Fusarium spp. pathogens. This gene codes for an unusual lectin with regions of high histidine and proline frequency and two apparent sugar binding moieties. Binding studies with yeast-produced versions indicated N-acetyl glucosamine residues are a likely target. When the gene was expressed transgenically in maize callus, reduced growth of pathogenic Fusarium species (up to 71%) and caterpillar pests (up to 65%) was noted compared to control transformants, and the degree of growth inhibition was associated with levels of the protein detected. Available sequence of the gene from other maize inbreds indicated it was often disrupted and likely to code for proteins with reduced function. Incorporation of functional versions of the gene into crops will likely assist with sustainable crop production by promoting enhanced pest resistance.

Genome-Guided Discovery of Antifungal Filipins from a Deep-Sea-Derived Streptomyces antibioticus.

Nine new (1-3, 5-8, 11, and 12; named filipins VI-XIV) and three known (4, 9, and 10) filipin-type polyene macrolides were isolated from the deep-sea-derived Streptomyces antibioticus OUCT16-23 using a genome-guided strategy coupled with bioassay. Their structures were elucidated based on the extensive MS and NMR spectroscopic analyses together with ECD calculations. In an antifungal assay, compounds 4, 5, and 7-10 showed different degrees of growth inhibition against Candida albicans with minimum inhibitory concentrations (MICs) of 1.56-12.5 μg/mL, by which the alkyl side-chain substitution affecting the activity was preliminarily studied. A biosynthetic pathway to 1-12 in S. antibioticus OUCT16-23 is also proposed.

Phytochemical analysis and antibacterial activity of Punica granatum L. seed extract against clinically isolated uropathogens

The discovery of plant based drugs and dietary supplements derived from plants has accelerated in recent years. Punica granatum L. is one such plant whose products are useful in the treatment of many diseases including urinary tract infections (UTI), since it is rich in various antioxidants like vitamin C, iron and phenolic compounds. Antioxidant rich fluids are known to prevent bacteria from adhering to the walls of the bladder and urethra; as a result UTI is cured or prevented. The present investigation aims to explore the urobactericidal activity of different solvent extracts of the seeds of P. granatum. In this study, P. granatum dried seed powder was extracted exhaustively with different solvents i.e. hexane, chloroform, acetone and methanol (HPG, CPG, APG and MPG). The presence of different phytochemicals in these extracts was assessed both qualitatively and quantitatively before evaluating their urobactericidal and uroprotective potency. It was found that seeds of pomegranate have many bioactive phytochemicals like terpenoids, steroids, tannins, coumarins, glycosides, flavonoids and phenolic compounds that contribute to its significant antibacterial activity and this was proved by various methods and the zone or degree of growth inhibition was measured against different uropathogens. It was observed that APG and MPG, which are rich in hydrophilic phytoconstituents have significant bactericidal activity in comparison to HPG and CPG, which are rich in hydrophobic compounds. Since, the active phytoconstituents present in P. granatum seed have potent urobactericidal activity, it can be further explored for its tremendous bioactive potentials and also attempts should be made to safeguard and cultivate this miraculous plant which would be beneficial to the society.

Extracellular Concentration of L-Cystine Determines the Sensitivity to System xc - Inhibitors.

Targeting the cystine/glutamate exchange transporter, system xc-, is a promising anticancer strategy that induces ferroptosis, which is a distinct form of cell death mediated by iron-dependent lipid peroxidation. The concentration of L-cystine in culture medium is higher than the physiological level. This study was aimed to evaluate the effects of L-cystine concentration on the efficacy of ferroptosis inducers in hepatocellular carcinoma cells. This study showed that treatment with sulfasalazine or erastin, a system xc- inhibitor, decreased the viability of Huh6 and Huh7 cells in a dose-dependent manner, and the degree of growth inhibition was greater in medium containing a physiological L-cystine concentration of 83 µM than in commercial medium with a concentration of 200 µM L-cystine. However, RSL3, a glutathione peroxidase 4 inhibitor, decreased cell viability to a similar extent in media containing both L-cystine concentrations. Sulfasalazine and erastin significantly increased the percentages of propidium iodide-positive cells in media with 83 µM L-cystine, but not in media with 200 µM L-cystine. Sulfasalazine- or erastin-induced accumulation of lipid peroxidation as monitored by C11-BODIPY probe was higher in media with 83 µM L-cystine than in media with 200 µM L-cystine. In contrast, the changes in the percentages of propidium iodide-positive cells and lipid peroxidation by RSL3 were similar in both media. These results showed that sulfasalazine and erastin, but not RSL3, were efficacious under conditions of physiological L-cystine concentration, suggesting that medium conditions would be crucial for the design of a bioassay for system xc- inhibitors.

Study of the antimicrobial and fungicidal activity of thiotriazoline and decamethoxinum as a potentially new model mixture for use of the oral mucosa

Today, diseases caused by pathogenic bacteria are the most dangerous, as they can not only affect the quality of human life, but also lead to death.According to the WHO, pathogenic bacteria namely, mycoses affect from 1/5 to 1/3 of the world's population, more than a third (37.8 %) of them cause yeast-like (Candida). Over the past 20 years, there has been a 15-fold increase in the frequency of infectious inflammatory diseases of candidiasis etiology.After examining the range of drugs on the pharmaceutical market of Ukraine and abroad, it was found that the following drugs of foreign origin are currently used for the treatment of these diseases: Methyluracil (Lekhim, Ukraine), Solkoseril (Birsfelden, Switzerland), Mexidol (PHARMASOFT, Moscow, RF).Based on the above it is seen that the range of drugs for the treatment of oral mucosa diseases is limited. All of the above shows the need for the creation of a new domestic drug exhibiting antimicrobial, fungicidal, reparative activity.The aim of our work is to create a new drug based on the model mixture of Thiotriazoline and Decamethoxinum, which exhibit antimicrobial, fungicidal, repertoire activity.Materials and methods. Thiotriazoline, decamethoxinum, model mixture. The studies were carried out by agar diffusion (well method) to study antimicrobial activity. Model mixtures with decamethoxinum were made from 0.5 to 5 mg; thiotriazoline – 200 mg. Antimicrobial activity of these model mixtures was carried out.Results. The model mixture of thiotriazoline and decamethoxinum in antimicrobial and fungicidal action was significantly superior to decamethoxinum by 54 % in the degree of growth inhibition of S. aureus, by 120 % in the degree of growth inhibition of E. coli, by 57 % in the degree of growth inhibition of P. aeruginosa, and by 108 % in the degree of growth retardation of C. albicans at 106 CFU/ml of medium.Conclusion. The model mixture of thiotriazoline and decamethoxinum exhibits high antimicrobial and fungicidal activity.

Methodology for compiling a microbial resistance passport for dairy farms

Abstract. The article presents the results of the work, the purpose of which was to create a microbial resistance passport for a dairy farm. Methods. Conducted studies of opportunistic pathogenic microflora in various technological areas, there were taken samples of feed, water, air, bedding, washings from the wool and mucous membranes of cows and calves, washings from surfaces, fences, technological equipment, and livestock care equipment. There were determined the frequency of occurrence and the proportion of microorganisms in the structure of the opportunistic microbiocenosis. Results. It was found that on all surveyed dairy farms, the nucleus of opportunistic microbiocenosis was represented by Ent. faecium, Ent. faecalis, S. aureus, S. epidermidis, S. saprophyticus, P. aeruginosa, P. vulgaris, P. mirabilis, Echerichia coli, Aspergillus spp. and C. albicans – the frequency of occurrence of these microorganisms in samples exceeded 15 %. We studied the two-year dynamics of the microbiocenoses composition on farms. It was found that the main nucleus of the microbiocenosis remained stable in species composition, and the percentage of stocks was subject to slight changes. There were carried out he studies of the sensitivity of all detected stocks to antibiotics, based on the results of which were compiled resistances profiles, methods were developed for the analysis of general indicators of microbial resistance throughout the enterprise and in individual technological areas, and were established the ways of spreading resistant stocks on the farm. On the basis of four criteria, including the effectiveness of the antibiotic against the target microorganism, the effectiveness against the non-target microorganism in vitro, the degree of growth inhibition, the minimum inhibitory concentration, the antibiotic susceptibility analysis of the main pathogenic microorganisms was carried out in points. The results obtained were used to predict the expected effectiveness of antibiotics in different technological areas of the farm. The novelty of the researches is in the development of an algorithm for compiling a passport of microbial resistance of a dairy farm, which includes analysis of opportunistic microbiocenosis, analysis of antibiotic sensitivity of microorganisms and prediction of the expected effectiveness of antibacterial drugs.

PHYTONCIDAL ACTIVITY OF ESSENTIAL OILS OF MEDICINAL PLANTS TO SOME STRAINS OF MOLD FUNGI

Herbal antiseptics with phytoncidal action, for example, plant essential oils, can be used indoors in the presence of people. The antifungal activity of essential oils of medicinal plants (anis, basil, clary cage, clove, coriander, jasmine, juniper, lavender, lemon, orchid, rose, rosemary, tea tree, wormwood, ylang ylang) was evaluated by the degree of growth inhibition of mold colonies Alternaria alternata , Aspergillus oryzae, Aspergillus flavus, and Cladosporium cladosporioides. Colonies incubated in Petri dishes with a drop of essential oil on the lid under control petrolatum. All essential oils in the experiment had phytoncidal properties. The oils were divided into groups: 1 with fungicidal action (coriander, jasmine, orchid, rose); 2 with high fungistatic activity to all strains (lavender, basil, tea tree oil); 3 with fungistatic properties against individual strains (C. cladosporioides rosemary and anise, A. alternata and A. flavus lemon, A. oryzae wormwood); 4 with a stimulating effect of the growth of colonies A. oryzae lemon oil.

A bendamustine resistance gene signature in diffuse large B-cell lymphoma and multiple myeloma.

Aim: Bendamustine is primarily used for treatment of indolent lymphomas but has shown efficacy in some patients with diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Molecular-based patient stratification for identification of resistant patients, who will benefit from alternative treatments, is important. The aim of this study was to develop a resistance gene signature (REGS) from bendamustine dose-response assays in cultures of DLBCL and MM cell lines, enabling prediction of bendamustine response in DLBCL and MM patients.Methods: Bendamustine response was determined in 14 DLBCL and 11 MM cell lines. Using baseline gene expression profiles and degree of growth inhibition after bendamustine exposure, a bendamustine REGS was developed and examined for the risk stratification potential in DLBCL (n = 971) and MM (n = 1,126) patients divided into prognostic subtypes.Results: Bendamustine resistance significantly correlated with resistance to cyclophosphamide in DLBCL and melphalan in MM cell lines. The bendamustine REGS showed significantly lower bendamustine resistance probabilities in DLBCL patients with GCB subtype tumors and in tumors of the differentiation dependent centrocyte and plasmablast subtypes. In MM patients, pre-BII classified tumors displayed high bendamustine resistance probabilities and the plasma cell subtype had lower bendamustine resistance probability than memory cells. Furthermore, tumors belonging to the 4p14, MAF, and D2 TC subclasses consistently displayed high bendamustine resistance probabilities.Conclusion: Significant differences in predicted response to bendamustine were found in molecular subtypes of DLBCL and MM, encouraging validation in prospective bendamustine-treated cohorts with available gene expression profiles and follow-up data.

SlMYB102, an R2R3-type MYB gene, confers salt tolerance in transgenic tomato

Salinity threatens the productivity of tomato (Solanum lycopersicum L.). R2R3-type MYB transcription factors are important regulators in response to environmental stress. Here, we analyzed the function of the tomato R2R3-type MYB gene SlMYB102. A transcriptional activation assay showed that SlMYB102 had transactivation activity in yeast. Promoter analysis showed that multiple stress-related elements were found in the promoter of SlMYB102. Furthermore, SlMYB102 was induced by osmotic stress, particularly by salt stress. The overexpression of SlMYB102 in tomato affected multiple parameters under salinity stress. Under long-term salt stress, the degree of growth inhibition was significantly reduced in the two overexpression (OE) lines. In addition, the two OE lines maintained a better K+/Na+ ratio, lower reactive oxygen species (ROS) generation (O2•− production rate and H2O2 content) and lower electrolytic leakage rates than the wild type (WT). The activity of ROS scavenging enzymes including superoxide dismutase, peroxidase, catalase and ascorbate peroxidase, and the accumulation of antioxidants (ascorbic acid and glutathione) and proline was higher in the two OE lines compared with WT. The qRT-PCR analysis confirmed that the transcript abundance of many salt stress-related genes (SlSOS1, SlSOS2, SlNHX3, SlNHX4, SlHAK5, SlCPK1 and SlCPK3) was upregulated in two OE lines under salt stress. Collectively, these results suggest that SlMYB102 participates in tomato tolerance through the regulation of a series of molecular and physiological processes.

Effects of spermidine and salinity stress on growth and biochemical response of paraquat‐susceptibe and ‐resistant goosegrass (Eleusine indica L.)

This study aimed to investigate the interaction effect of spermidine (Spd) and salinity stress on growth, photosynthetic rate, antioxidant system and free polyamines (PAs) contents of goosegrass (Eleusine indica L.) seedlings. E. indica was raised in a growth chamber under normal and toxic salt stress (100 mM of NaCl) and sprayed with 0 and 1.00 mM of Spd. The degree of growth inhibition caused by salt stress was lower in a paraquat‐resistant (R) biotype compared to a paraquat‐susceptible (S) biotype. Salt stress significantly elevated the accumulation of malondialdehyde, electrolyte leakage and proline and resulted in the degradation of chlorophyll; reduction in chlorophyll fluorescence; and a decrease in photosynthetic rate, relative water content and biomass. Spd‐treated plants maintained higher activities of antioxidant enzymes (catalase, superoxide dismutase and peroxidase), a greater rate of photosynthesis and lower osmotic pressure than untreated plants in the S biotype. Endogenous Spd content was reduced significantly in response to salt stress in both biotypes, but free PAs content in the S biotype was remarkably enhanced with exogenous Spd application under normal or salinity stress conditions. The result indicated that the S biotype was more sensitive to salinity than the R biotype; meanwhile, exogenous Spd maybe play an important role in protecting S biotype plants from salt stress.

Growth inhibitory activities of extracts from peels of five species of citrus fruit on bacterial isolates obtained from rotten tomato fruits.

This study was undertaken to verify the efficacies of phytochemical extracts of citrus fruit peels obtained from Citrus sinensis, Citrus reticulata, Citrus limonum, Citrus aurantifolia and Citrus vitis against isolates of tomato rot bacteria. Results of this study provide the much needed less hazardous, cheap and readily available means of controlling or managing bacterial diseases of postharvest tomato fruits to reduce the huge economic losses often incurred by tomato fruits dealers and farmers. Solvent extracts were characterized for presence of constituent active compounds, flavonoids, tannins, terpenes, cardiac glycosides, anthraquinones, saponins and alkaloids. Pseudomonas spp., Klebsiella spp. and Escherichia coli were isolated from rotten tomato fruits using McConkey, Blood and Peptone Sucrose agar media. Isolates were subjected to sensitivity test with 10%, 20%, 30% and 40% concentrations (volume by volume) of the different extracts, respectively. All the concentrations showed different degrees of growth inhibition on the test organisms. The study confirmed that phytochemical extracts from peels of citrus fruits are efficacious against tomato fruit rot bacteria and therefore have a good promise for sustainable control of bacterial rot disease of tomato fruits.

Concomitant attenuation of HMG-CoA reductase expression potentiates the cancer cell growth-inhibitory effect of statins and expands their efficacy in tumor cells with epithelial characteristics.

HMG-CoA reductase (HMGCR) inhibitors, statins, are potent cholesterol reducing drugs that exhibit anti-tumor effects in vitro and in animal models, including attenuation of metastasis formation, and their use correlates with reduced cancer-specific mortality in retrospective human cohort studies. However, E-cadherin expressing epithelial- and mixed epithelial-mesenchymal cancer cell lines (reflective of primary and outgrowing metastatic tumor cells, respectively) require higher statin concentrations than mesenchymal-like tumor cells (reflective of in-circulation metastatic tumor cells) to achieve the same degree of growth inhibition. Here, we show that attenuation of HMGCR expression in the presence of atorvastatin leads to stronger growth inhibition than dual target blockade of the mevalonate pathway in relatively statin resistant cell lines, mainly through inhibition of protein prenylation pathways. Thus, combined inhibition of the mevalonate pathway's rate-limiting enzyme, HMGCR, can improve atorvastatin's growth inhibitory effect on epithelial- and mixed mesenchymal-epithelial cancer cells, a finding that may have implications for the design of future anti-metastatic cancer therapies.

Synthesis, theoretical studies, and effect on the photosynthetic electron transport of trifluoromethyl arylamides.

The photosynthetic apparatus is targeted by various herbicides, including several amides such as diuron and linuron. Considering the need for the discovery of new active ingredients to cope with weed resistance, the synthesis of a series of trifluoromethyl aryl amides is herein described whose inhibitory properties were assessed in vitro on the photosynthetic electron transport chain, and in vivo on the growth of a model cyanobacterial strain. Theoretical studies were also carried out. Starting with 1-fluoro-2-nitro-4-(trifluoromethyl) benzene, the preparation of the amides was achieved via a three-step sequence, namely nucleophilic aromatic substitution, reduction with SnCl2 /HCl, and acylation reactions. The measurement of ferricyanide reduction by functionally intact spinach chloroplasts showed that several derivatives are capable of inhibiting the photosynthetic apparatus. The most active amides presented IC50 values close to 1 μmol L-1 , and showed the presence of a 4-bromophenyl group as a common structural feature. The addition of these brominated amides to the culture medium of a model cyanobacterial strain, Synechococcus elongatus PCC 6301, caused various degrees of growth inhibition. Theoretical studies (molecular modeling and quantitative structure-activity relationship) of all amides and their comparison with some known herbicides confirmed these experimental findings and provided more in-depth information about the possible molecular target of these compounds. Trifluoromethyl amides herein described, which were shown to act at the PSII level, may represent a novel scaffold to be exploited aiming at the development of new active ingredients for weed control. © 2017 Society of Chemical Industry.