Unorthodox synthesis, biological activity and DFT studies of novel and multifunctionalized naphthoxocine derivatives

A new promising protocol has been developed for the synthesis of scarce oxocine derivatives 3a–e and 6 through addition of amine-based nucleophiles such as hydroxylamine hydrochloride, primary amine and hydrazide to chromonylidene benzothiazol-2-ylacetonitrile 2 in refluxing dioxane under metal free reaction conditions in moderate to good yields. Other nitrogen nucleophiles such as piperidine, hydrazine and thiosemicarbazide failed to afford the corresponding oxocinols, and instead pyridine derivatives 7, 8 and 10 were obtained exclusively. Predictive study for the biological activities using PASS (prediction of activity spectra for biologically active substances) online software showed optimistic activities for oxocinols 3a–e in the treatment of cancer, influenza A and microbial infections. Additionally, DFT studies of oxocine derivatives 3a–e and 6 indicated the presence of required thermodynamics parameters for the application in dye-sensitized solar cells (DSSCs)

Synthesis of novel naphthalene-heterocycle hybrids with potent antitumor, anti-inflammatory and antituberculosis activities

Multitarget-directed drugs (hybrid drugs) constitute an efficient avenue for the treatment of multifactorial diseases. In this work, novel naphthalene hybrids with different heterocyclic scaffolds such as nicotinonitrile, pyran, pyranopyrazole, pyrazole, pyrazolopyridine, and azepine were efficiently synthesized via tandem reactions of 3-formyl-4H-benzo[h]chromen-4-one 1 with different nucleophilic reagents. Analysis of these hybrids using PASS online software indicated different predicted biological activities such as anticancer, antimicrobial, antiviral, antiprotozoal, anti-inflammatory, etc. By focusing on antitumor, anti-inflammatory, and antituberculosis activities, many compounds revealed remarkable activities. While 3c, 3e, and 3h were more potent than doxorubicin in the case of HepG-2 cell lines, 3a–e, 3i, 6, 8, 10, 11, and 12b were more potent in the case of MCF-7. Moreover, compounds 3c, 3h, 8, 10, 3d, and 12b manifested superior activity and COX-2 selectivity to the reference anti-inflammatory Celecoxib. Regarding antituberculosis activity, 3c, 3d, and 3i were found to be the most promising with MIC less than 1 mg mL–1. The molecular docking studies showed strong polar and hydrophobic interactions with the novel naphthalene-heterocycle hybrids that were compatible with experimental evaluations to a great extent

Rebalancing Nutrients, Reinforcing Antioxidant and Osmoregulatory Capacity, and Improving Yield Quality in Drought-Stressed <i>Phaseolus vulgaris</i> by Foliar Application of a Bee-Honey Solution

Bee-honey solution (BHS) is considered a plant growth multi-biostimulator because it is rich in osmoprotectants, antioxidants, vitamins, and mineral nutrients that can promote drought stress (DtS) resistance in common bean plants. As a novel strategy, BHS has been used in a few studies, which shows that the application of BHS can overcome the stress effects on plant productivity and can contribute significantly to bridging the gap between agricultural production and the steady increase in population under climate changes. Under sufficient watering (SW (100% of crop evapotranspiration; ETc) and DtS (60% of ETc)), the enhancing impacts of foliar application with BHS (0%, 0.5%, 1.0%, and 1.5%) on growth, productivity, yield quality, physiological-biochemical indices, antioxidative defense ingredients, and nutrient status were examined in common bean plants (cultivar Bronco). DtS considerably decreased growth and yield traits, green pod quality, and water use efficiency (WUE); however, application of BHS at all concentrations significantly increased all of these parameters under normal or DtS conditions. Membrane stability index, relative water content, nutrient contents, SPAD (chlorophyll content), and PSII efficiency (Fv/Fm, photochemical activity, and performance index) were markedly reduced under DtS; however, they increased significantly under normal or DtS conditions by foliar spraying of BHS at all concentrations. The negative impacts of DtS were due to increased oxidants [hydrogen peroxide (H2O2) and superoxide (O2•−)], electrolyte leakage (EL), and malondialdehyde (MDA). As a result, the activity of the antioxidant system (ascorbate peroxidase, glutathione reductase, catalase, superoxide dismutase, α-tocopherol, glutathione, and ascorbate) and levels of osmoprotectants (soluble protein, soluble sugars, glycine betaine, and proline) were increased. However, all BHS concentrations further increased osmoprotectant and antioxidant capacity, along with decreased MDA and EL under DtS. What is interesting in this study was that a BHS concentration of 1.0% gave the best results under SW, while a BHS concentration of 1.5% gave the best results under DtS. Therefore, a BHS concentration of 1.5% could be a viable strategy to mitigate the DtS impairment in common beans to achieve satisfactory growth, productivity, and green pod quality under DtS

Physiological and Biochemical Mechanisms of Exogenously Applied Selenium for Alleviating Destructive Impacts Induced by Salinity Stress in Bread Wheat

Salinity is a major abiotic stress that poses great obstacles to wheat production, especially in arid regions. The application of exogenous substances can enhance plant salt tolerance and increase its productivity under salinity stress. This work aimed to assess the mechanisms of selenium (Se) at different concentrations (2, 4 and 8 μM SeCl2) to mitigate hazardous impacts of salt toxicity at physiological, biochemical and agronomic levels in bread wheat. The results displayed that Se foliar application increased chlorophyll content, net photosynthetic rate, transpiration rate, stomatal conductance, relative water content, membrane stability index, excised leaf water retention, proline, total soluble sugars, Ca content, K content, antioxidant enzyme activities and non-enzymatic antioxidant compounds compared to untreated plants. On the other hand, Se application decreased the content of Na, hydrogen peroxide and superoxide contents. Accordingly, our findings recommend exogenous Se application (in particular 8 μM) to alleviate the deleterious effects induced by salinity stress and improve wheat yield attributes through enhancing antioxidant defense systems and photosynthetic capacity

The importance of propolis in alleviating the negative physiological effects of heat stress in quail chicks

<div><p>Heat stress is one of the most detrimental confrontations in tropical and subtropical regions of the world, causing considerable economic losses in poultry production. Propolis, a resinous product of worker honeybees, possesses several biological activities that could be used to alleviate the deleterious effects of high environmental temperature on poultry production. The current study was aimed at evaluating the effects of propolis supplementation to Japanese quail (<i>Coturnix coturnix japonica</i>) diets on the production performance, intestinal histomorphology, relative physiological and immunological parameters, and selected gene expression under heat stress conditions. Three hundred one-day-old Japanese quail chicks were randomly distributed into 20 wired-cages. At 28 d of age, the birds were divided into 2 temperature treatment groups; a normal at 24°C (C group) and a heat stress at 35°C (HS group). The birds in each group were further assigned to 2 subgroups; one of them was fed on a basal diet without propolis supplementation (-Pr subgroup) while the other was supplemented with propolis (+Pr subgroup). Production performance including body weight gain, feed intake and feed conversion ratio were measured. The intestinal histomorphological measurements were also performed for all treatment groups. Relative physiological parameters including body temperature, corticosterone hormone level, malondialdehyde (MDA) and free triiodothyronine hormone (fT3), as well as the relative immunological parameters including the total white blood cells count (TWBC’s), heterophil/lymphocyte (H/L) ratio and lymphocyte proliferation index, were also measured. Furthermore, the mRNA expression for toll like receptor 5 (TLR5), cysteine-aspartic protease-6 (CASP6) and heat shock proteins 70 and 90 (Hsp70 and Hsp90) genes was quantified in this study. The quail production performance was significantly (P<0.05) impaired by HS treatment, while Pr treatment significantly improved the quail production performance. The villus width and area were significantly (P<0.05) lower in the HS compared to the C group, while Pr treatment significantly increased crypts depth of quail. A negative impact of HS treatment was observed on the physiological status of quail; however, propolis significantly alleviated this negative effect. Moreover, quail of the HS group expressed lower immunological parameters than C group, while propolis enhanced the immune status of the quail. The relative mRNA expression of TLR5 gene was down-regulated by HS treatment while it was up-regulated by the Pr treatment. Furthermore, the positive effects of propolis in HS-quail were evidenced by normalizing the high expressions of CASP6 and Hsp70 genes when compared to the C group. Based on these results, the addition of propolis to quail diets as a potential nutritional strategy in order to improve their performance, especially under heat stress conditions, is recommended.</p></div

Least square means for the histomorphological measurements of small intestines as affected by heat stress and dietary propolis supplementation in Japanese quail.

<p>Least square means for the histomorphological measurements of small intestines as affected by heat stress and dietary propolis supplementation in Japanese quail.</p

Least square means for some physiological parameters as affected by heat stress and dietary propolis supplementation in Japanese quail.

<p>Least square means for some physiological parameters as affected by heat stress and dietary propolis supplementation in Japanese quail.</p

Least square means for the production performance traits as affected by heat stress and dietary propolis supplementation in Japanese quail.

<p>Least square means for the production performance traits as affected by heat stress and dietary propolis supplementation in Japanese quail.</p

The hepatic relative expression of TLR5, CASP6, Hsp70 and Hsp90 genes as affected by heat stress and dietary propolis supplementation in Japanese quail.

<p>Bars express the means ± standard error of means (n = 10). C: control groups that were exposed to 24°C; HS: heat stress groups that were exposed to 35°C; -Pr: subgroups without dietary propolis supplementation; +Pr: subgroups with dietary propolis supplementation. ^a-b Means within the same gene with different superscripts are significantly different (P<0.05). The main effects of heat stress (HS), propolis (Pr) and their interaction (HSxPr) are provided for each gene in the table (S: significant; NS: non-significant).</p

Least square means for some immunological parameters as affected by heat stress and dietary propolis supplementation in Japanese quail.

<p>Least square means for some immunological parameters as affected by heat stress and dietary propolis supplementation in Japanese quail.</p