QSAR studies on the human sirtuin 2 inhibition by non-covalent 7,5,2-anilinobenzamide derivatives

Abstract

Sirtuin 2 is a key enzyme in gene expression regulation that is often associated with tumor proliferation control and therefore is a relevant anticancer drug target. Anilinobenzamide derivatives have been discussed as selective sirtuin 2 inhibitors and can be developed further. In the present study, hologram and three-dimensional quantitative structure–activity relationship (HQSAR and 3D-QSAR) analyses were employed for determining structural contributions of a compound series containing human sirtuin-2-selective inhibitors that were then correlated with structural data from the literature. The final QSAR models were robust and predictive according to statistical validation (q² and r²_pred values higher than 0.85 and 0.75, respectively) and could be employed further to generate fragment contribution and contour maps. 3D-QSAR models together with information about the chemical properties of sirtuin 2 inhibitors can be useful for designing novel bioactive ligands.

Communicated by Ramaswamy H. Sarma     

On the release of fluoride from biofilm reservoirs during a cariogenic challenge: an in situ study

Abstract

Biofilm fluoride reservoirs may be a source of fluoride to the fluid phase during a sugar challenge reducing tooth mineral loss. However, the evidence for that is conflicting and has not been studied in biofilms containing different fluoride levels. In order to test fluoride release from biofilms with distinct fluoride concentrations, biofilms were grown in situ exposed to a combination of placebo, calcium and fluoride rinses forming biofilms with no (fluoride-free rinses), low (fluoride-only rinses) or high (calcium followed by fluoride rinses) fluoride concentrations, and collected before and 5?min after a sucrose challenge. Rinsing with fluoride increased fluoride concentration in the biofilm (p?<?0.05), mainly when a calcium pre-rinse was used before the fluoride (p?<?0.05). However, after a sugar challenge, no significant increase in the biofilm fluid fluoride concentration was observed, even in the fluoride-rich biofilms (p?>?0.05). Fluoride-rich biofilms do not release fluoride to the fluid phase during a sugar challenge.     

Development of a novel anti-biofilm peptide derived from profilin of Spodoptera frugiperda

Abstract

Candida yeast infections are the fourth leading cause of death worldwide. Peptides with antimicrobial activity are a promising alternative treatment for such infections. Here, the antifungal activity of a new antimicrobial peptide—PEP-IA18—was evaluated against Candida species. PEP-IA18 was designed from the primary sequence of profilin, a protein from Spodoptera frugiperda, and displayed potent activity against Candida albicans and Candida tropicalis, showing a minimum inhibitory concentration (MIC) of 2.5?µM. Furthermore, the mechanism of action of PEP-IA18 involved interaction with the cell membrane (ergosterol complexation). Treatment at MIC and/or 10?×?MIC significantly reduced biofilm formation and viability. PEP-IA18 showed low toxicity toward human fibroblasts and only revealed hemolytic activity at high concentrations. Thus, PEP-IA18 exhibited antifungal and anti-biofilm properties with potential applicability in the treatment of infections caused by Candida species.     

Characterization and removal of biofouling from reverse osmosis membranes (ROMs) from a desalination plant in Northern Chile,using Alteromonas sp. Ni1-LEM supernatant

Abstract

Biofouling control in reverse osmosis membranes (ROMs) is challenging due to the high cost of treatments, and reduction in the life of ROMs. This study characterizes the biofouling in the ROMs from a desalination plant and reports its effective removal using the supernatant obtained from Alteromonas sp. strain Ni1-LEM. The characterization of the bacterial community revealed that the most abundant taxa in ROMs were the genera Fulvivirga and Pseudoalteromonas, and unclassified species of the families Flavobacteriaceae and Sphingomonadaceae. This bacterial community significantly decreased upon treatment with the supernatant from Alteromonas sp. Ni1-LEM, resulting in the prevalence of the genus Pseudoalteromonas. Furthermore, this bacterial supernatant significantly inhibited cell adhesion of seven benthic microalgae isolated from ROMs as well as promoting cell detachment of the existing microbial biofilms. The study showed that the extracellular supernatant modified the conformation of extracellular polymeric substances (EPS) in the biofouling of ROMs without any biocidal effects.     

Water deficit tolerance in sugarcane is dependent on the accumulation of sugar in the leaf

Sugarcane productivity is severely affected by the occurrence of water deficit in the field, causing inhibition of growth and sugar production. Evaluating physiological responses of sugarcane under water deficit conditions is essential to understand physiological variables responsible for reaching homeostasis. Therefore, we analysed physiological traits of two sugarcane genotypes, RB835486 (Tolerant) and RB855453 (Susceptible), under water deficit conditions: well-watered (WW-Control), water deficit (WD) and rewatered (RW). The physiological response was evaluated using linear regression and multivariate analysis. Some characteristics such as water potential in leaves, photosynthesis, chlorophyll fluorescence, chlorophyll index, sucrose and starch contents did not show differences between the genotypes under water deficit conditions. However, the tolerant genotype showed increased reducing sugars content in the leaves, whereas the susceptible genotype had increased non-photochemical quenching (qN). After rewatering, the susceptible sugarcane genotype showed higher electron transport rate (ETR) and efficiency of PSII (Y). Multivariate analysis revealed that non-photochemical quenching and reducing sugars in the leaves were physiological variables responsible for reaching homestasis under water deficit conditions. Therefore, the reducing sugars concentration should be considered a physiological variable responsible for the adjustment made by the tolerant sugarcane genotype when submitted to water deficit.     

Expression of the Arcelin 1 gene from Phaseolus vulgaris L. in cowpea seeds (Vigna unguiculata L.) confers bruchid resistance

Persistent decrease in the productivity of cowpea (Vigna unguiculata L.) has been partly due to attack by bruchids including Zabrotes subfasciatus and Callosobruchus maculatus. Resistance to these insects in Phaseolus vulgaris L. has been shown to be associated with arcelins, a family of seed proteins encoded by a multigenic family of lectins on the APA locus. In this work, we report the construction of an expression vector containing Arc1 gene isolated from P. vulgaris and introduced into cowpea as a strategy to confer resistance to insect attack. Following transformation and selection, feeding experiments in which C. maculatus and Z. subfasciatus were fed with transgenic (L3 and L5) and non-transgenic (control) grains showed that introduced gene protected the transgenic line. Significant differences (p < .05 and p < .01) were found in the number of eggs laid, the number of emerging insects and the loss of grain mass in L3, compared with control, for both insects. Similar observations were made in L5 with the exception of the number of laid eggs. The strategy here described may form the basis for the development of a cowpea variety tolerant to bruchids in a crop cultivated by farmers throughout Latin America and Africa.     

Feeding behavior of Brevicoryne brassicae in resistant and susceptible collard greens genotypes: interactions among morphological and chemical factors

The cabbage aphid, Brevicoryne brassicae (L.) (Hemiptera: Aphididae), is distributed throughout the tropical and subtropical areas of the world. The main crops attacked by B. brassicae are cabbage, collard greens, broccoli, Brussels sprouts, and cauliflower. To survive the attack of pest insects, plants have evolved various resistance mechanisms that may affect pest feeding behavior. The use of electronic monitoring through EPG (electrical penetration graph) can help characterize and distinguish the resistance mechanisms involved. This study evaluated the feeding behavior of B. brassicae in eight genotypes of collard greens, Brassica oleraceae L. var. acephala (Brassicaceae), exhibiting antixenosis and/or antibiosis resistance to this insect. Possible correlations were established between the glucosinolate levels, the hardness, and the epicuticular wax on the leaves vs. aphid feeding behavior. On the genotypes 22V, 5E, and 27VA, for which many ‘potential drop’ waves were performed, aphid development was slower, indicating antixenosis as resistance type. Aphids on the genotypes 22V and 24X required more time until accessing the phloem, also suggesting antixenosis as resistance category. Genotypes 22V and PE had hard leaves, which also points at antixenosis. Genotypes 20T and HS had higher total wax and wax mg⁻¹. Feeding parameters on ARI and 24X were similar to those observed on HS; antibiosis is likely to be the predominant resistance category of this germplasm. Because HS was considered as a susceptible standard genotype in this study, a higher gluconapin amount indicates that this compound does not influence cabbage aphid feeding behavior. The present study confirms that analysis of the physical and chemical aspects of collard greens genotypes by the EPG technique can provide a useful approach for the study of plant resistance to cabbage aphids.     

Loss and rescue of osteocalcin and osteopontin modulate osteogenic and angiogenic features of mesenchymal stem/stromal cells

Noncollagenous proteins in the bone extracellular matrix, such as osteocalcin (OC) and osteopontin (OPN), inherent to evolution of bone as a skeletal tissue, are known to regulate bone formation and mineralization. However, the fundamental basis of this regulatory role remains unknown. Here, for the first time, we use mouse mesenchymal stem/stromal cells (MSC) lacking both OC and OPN to investigate the mechanistic roles of OC and OPN on the proliferation capacity and differentiation ability of MSC. We found that the loss of OC and OPN reduces stem cells self-renewal potential and multipotency, affects their differentiation into an osteogenic lineage, and impairs their angiogenic potential while maintaining chondrogenic and adipogenic lineages. Moreover, loss of OC and OPN compromises the extracellular matrix integrity and maturation, observed by an unexpected enhancement of glycosaminoglycans content that are associated with a more primitive skeletal connective tissue, and by a delay on the maturation of mineral species produced. Interestingly, exogenously supplemented OC and OPN were able to rescue MSC proliferative and osteogenic potential along with matrix integrity and mineral quality. Taken together, these results highlight the key contributions of OC and OPN in enhancing osteogenesis and angiogenesis over primitive connective tissue, and support a potential therapeutic approach based on their exogenous supplementation.