Expanding roles of cross-talk between hydrogen sulfide and nitric oxide under abiotic stress in plants.

Abiotic stress such as salt, heavy metals, drought, temperature, and others can affect plants from seed germination to seedling growth to reproductive maturity. Abiotic stress increases reactive oxygen species and lowers antioxidant enzymes in plants resulted the plant tolerance ability against stress conditions decrease. Hydrogen sulfide (H2S) and nitric oxide (NO) are important gasotransmitters involved in seed germination, photosynthesis, growth and development, metabolism, different physiological processes and functions in plants. In plants, various enzymes are responsible for the biosynthesis of both H2S and NO via both enzymatic and non-enzymatic pathways. They also mediate post-translation modification, such as persulfidation, and nitrosylation, which are protective mechanisms against oxidative damage. They also regulate some cellular signalling pathways in response to various abiotic stress. H2S and NO also stimulate biochemical reactions in plants, including cytosolic osmoprotectant accumulation, reactive oxygen species regulation, antioxidant system activation, K+ uptake, and Na+ cell extrusion or vacuolar compartmentation. In this review, we summarize how H2S and NO interact with each other, the function of both H2S and NO, the mechanism of biosynthesis, and post-translational modification under different abiotic stress. Our main emphasis was to find the cross-talk between NO and H2S and how they regulate genes in plants under abiotic stress.

Synergizing structure and function: Cinnamoyl hydroxamic acids as potent urease inhibitors.

The current investigation encompasses the structural planning, synthesis, and evaluation of the urease inhibitory activity of a series of molecular hybrids of hydroxamic acids and Michael acceptors, delineated from the structure of cinnamic acids. The synthesized compounds exhibited potent urease inhibitory effects, with IC50 values ranging from 3.8 to 12.8 µM. Kinetic experiments unveiled that the majority of the synthesized hybrids display characteristics of mixed inhibitors. Generally, derivatives containing electron-withdrawing groups on the aromatic ring demonstrate heightened activity, indicating that the increased electrophilicity of the beta carbon in the Michael Acceptor moiety positively influences the antiureolytic properties of this compounds class. Biophysical and theoretical investigations further corroborated the findings obtained from kinetic assays. These studies suggest that the hydroxamic acid core interacts with the urease active site, while the Michael acceptor moiety binds to one or more allosteric sites adjacent to the active site.

Ionomic responses of hydroponic-grown basil (Ocimum basilicum L.) to cadmium long-time exposure.

The ionomic response of basil leaves, stems, and roots to Cd2+ was evaluated in seedlings grown in a hydroponic system for 15 days. Ions were quantified by the inductively coupled plasma-mass spectrometry (ICP-MS). Cd accumulated mainly in roots, while Be, Li, Ca, Mg, and Sr in leaves, and K and Mn in stems. Compared to the control group, basil seedlings treated with Cd2+ accumulated higher Ca, Cu, Mn, Sr, and Zn contents in roots, even when exposed at low levels. Pearson positive correlations between Cd and essential and nonessential elements were mostly observed in leaves and roots (P < 0.05). On the other hand, negative correlations were observed mainly in stems with all elements except Ba, Li, Sr, and Zn. Principal component analysis showed an ionomic discrimination between leaves, stems, and roots, with Cd strongly correlated to Zn, Cu, and Sr.

How Does LC/MS Compare to UV in Coffee Authentication and Determination of Antioxidant Effects? Brazilian and Middle Eastern Coffee as Case Studies.

Coffee is a popular beverage owing to its unique flavor and diverse health benefits. The current study aimed at investigating the antioxidant activity, in relation to the phytochemical composition, of authenticated Brazilian green and roasted Coffea arabica and C. robusta, along with 15 commercial specimens collected from the Middle East. Ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-ESI-HRMS) and UV spectrometry were employed for profiling and fingerprinting, respectively. With the aid of global natural product social molecular networking (GNPS), a total of 88 peaks were annotated as belonging to different chemical classes, of which 11 metabolites are reported for the first time in coffee seeds. Moreover, chemometric tools showed comparable results between both platforms, with more advantages for UV in the annotation of roasting products, suggesting that UV can serve as a discriminative tool. Additionally, antioxidant assays coupled with the UHPLC-ESI-HRMS dataset using partial least-squares discriminant analysis (PLS-DA) demonstrated that caffeoylquinic acid and caffeine were potential antioxidant markers in unroasted coffee versus dicaffeoyl quinolactone and melanoidins in roasted coffee. The study presents a multiplex metabolomics approach to the quality control of coffee, one of the most consumed beverages.

Interactions between As and Se upon long exposure time and effects on nutrients translocation in golden flaxseed seedlings.

Se is a beneficial nutrient for some plant species, while As is considered a toxic element, even at low concentrations. This study investigated the interaction between As and Se on golden flaxseed (Linum usitatissimum L.) seedlings to better understand the extent of Se in the mitigation of As uptake and translocation. In addition, co-exposure experiments allowed to determine how As and Se affected absorption and distribution of the essential micronutrients Fe, Zn and Mn. Seedlings were cultivated in a 10 % v v-1 Hoagland solution supplemented with AsV, SeIV, SeVI or AsV + SeIV at different concentrations. SeVI presented the highest toxicity and translocation factor. The toxicity of AsV was attenuated by SeIV, which stimulated As uptake and translocation. SeIV reduced As accumulation, establishing a tolerance mechanism. Only a high concentration of As (200 µmol L-1) led to leaf chlorosis or seedling death, independently of co-exposure with Se species. Co-exposure also altered the uptake of Fe, Zn and Mn, without affecting As translocation from roots to shoot. In general, the interaction of As with Se was beneficial for golden flaxseed seedlings, when compared to the effects of As solely.

Antiureolytic Activity of Substituted 2,5-Diaminobenzoquinones.

A series of 2,5-bis(alkyl/arylamino)-1,4-benzoquinones (1-12) were investigated in vitro for their potential to inhibit the activity of jack bean urease. Compounds 1-6, 8, 9, 11 and 12 effectively inhibited the jack bean urease activity by 90.8 % when tested at 5 µm, whereas 7 and 10 had relatively little effect. The IC50 for most compounds was in the nanomolar range (31.4 nm and 36.0 nm for 2 and 8, respectively). The mechanism of enzyme inhibition shown by 2 and 8 is typical of mixed-type inhibitors, whose affinity for the active site is over 6- and 2-fold higher (Ki =30.0 and 22.8 nm, for 2 and 8, respectively) than that of an allosteric site. Molecular docking studies revealed that both 2 and 8 establish hydrogen bonds with the amino acids residues Asp494, Met588, His593 and Ala636 in the active site of jack bean urease. These results indicate that such aminoquinones are useful leads for the development of more efficient urease inhibitors of wider utility.

Pre-emergence application of (thio)urea analogues compromises the development of the weed species Bidens pilosa, Urochloa brizantha, and Urochloa decumbens.

Invasive species (weeds) contribute to great losses in crop productivity, and one of the strategies for controlling their distribution in the field involves the use of herbicides. However, the development of new formulations for the control of weeds is challenged by environmental issues, increases in the resistance of weeds to herbicides, and poor selectivity of herbicides towards invasive species. Here, by using pre-emergence experiments, we assessed the phytotoxicity of two (thio)urea analogues (2A10 and 2B2) against the weed species Bidens pilosa (a dicot), Urochloa brizantha and Urochloa decumbens (monocots). Similar to diuron (400 µM), which is a commercial urea analogue herbicide, the urea analogue 2A10 (>200 µM) was lethal to B. pilosa. Although 2A10 failed to disrupt the germination of U. brizantha seeds, this compound (≥600 µM) inhibited the accumulation of chlorophyll a and b and carotenoids and resulted in the development of seedlings that presented relatively short roots and small, chlorotic leaves. Moreover, the thiourea analogue 2B2 (≥600 µM) reduced the germination percentage of U. decumbens seeds and delayed their germination, and at a concentration of 800 µM, this analogue impaired root growth and blocked the formation of lateral roots. The presence of an oxygen atom in the urea moiety of the 2A10 structure is critical for its marked activity against B. pilosa seeds, as 2B2 bears a sulphur atom instead and marginally inhibits seed germination. Neither 2A10 nor 2B2 was toxic to the non-weed species Lactuca sativa (lettuce; a dicot), and the latter even exerted beneficial effects by stimulating leaf expansion. Therefore, the evaluated (thio)urea analogues are promising for the design and development of new phytotoxic compounds for the pre-emergent control of the spread of B. pilosa (2A10) or the post-emergence control of U. brizantha (2A10) and U. decumbens (2B2).

4-Methylbenzenecarbothioamide, a hydrogen sulfide donor, inhibits tumor necrosis factor-α and CXCL1 production and exhibits activity in models of pain and inflammation.

The gasotransmitter hydrogen sulfide (H2S) is known to regulate many pathophysiological processes. Preclinical assays have demonstrated that H2S donors exhibit anti-inflammatory and antinociceptive activities, characterized by reduction of inflammatory mediators production, leukocytes recruitment, edema and mechanical allodynia. In the present study, the effects induced by 4-methylbenzenecarbothioamide (4-MBC) in models of pain and inflammation in mice, the mechanisms mediating such effects and the H2S-releasing property of this compound were evaluated. 4-MBC spontaneously released H2S in vitro in the absence of organic thiols. Intraperitoneal (i.p.) administration of 4-MBC (100 or 150 mg/kg) reduced the second phase of the nociceptive response induced by formaldehyde and induced a long lasting inhibitory effect on carrageenan mechanical allodynia. 4-MBC antiallodynic effect was not affected by previous administration of naltrexone or glibenclamide. 4-MBC (50, 100 or 150 mg/kg, i.p.) induced a long lasting inhibitory effect on paw edema induced by carrageenan. The highest dose (150 mg/kg, i.p.) of 4-MBC inhibited tumor necrosis factor-α and CXCL1 production and myeloperoxidase activity induced by carrageenan. Mechanical allodynia and paw edema induced by carrageenan were not inhibited by the 4-MBC oxo analogue (p-toluamide). In summary, 4-MBC, an H2S releasing thiobenzamide, exhibits antinociceptive and anti-inflammatory activities. These activities may be due to reduced cytokine and chemokine production and neutrophil recruitment. The H2S releasing property is likely essential for 4-MBC activity. Our results indicate that 4-MBC may represent a useful pharmacological tool to investigate the biological roles of H2S.

Nitric oxide precursors prevent Al-triggered auxin flow inhibition in Triticum aestivum roots.

Aluminum (Al) is an element widely distributed in soils, even though Al3+ is one of the most detrimental cations to plant growth. The effect of nitric oxide (NO) precursors on indole-3-acetic acid (IAA) flow towards roots upon Al treatment is herein reported using two Triticum aestivum (wheat) cultivars with recognized differential Al tolerance. Roots of Al-tolerant seedlings with no treatment (control) accumulated higher amounts of NO than Al-sensitive ones. The treatment with Al further stimulated NO production in root cells while root exposure to NO3 -, L-arginine (Arg) or the NO donor S-nitrosoglutathione (GSNO) decreased both Al and lipid peroxide accumulation in both cultivars. Regardless of the cultivar, NO3 -, Arg or GSNO prevented the blockage of IAA flow towards roots. Overall, the treatment of wheat roots with NO precursors prior to Al treatment effectively guarantees normal IAA flow towards roots, a condition that favors the organ's growth and development.

A minireview on what we have learned about urease inhibitors of agricultural interest since mid-2000s.

World population is expected to reach 9.7 billion by 2050, which makes a great challenge the achievement of food security. The use of urease inhibitors in agricultural practices has long been explored as one of the strategies to guarantee food supply in enough amounts. This is due to the fact that urea, one of the most used nitrogen (N) fertilizers worldwide, rapidly undergoes urease-driven hydrolysis on soil surface yielding up to 70% N losses to environment. This review provides with a compilation of what has been done since 2005 with respect to the search for good urease inhibitors of agricultural interests. The potential of synthetic organic molecules, such as phosphoramidates, hydroquinone, quinones, (di)substituted thioureas, benzothiazoles, coumarin and phenolic aldehyde derivatives, and vanadium-hydrazine complexes, together with B, Cu, S, Zn, ammonium thiosulfate, silver nanoparticles, and oxidized charcoal as urease inhibitors was presented from experiments with purified jack bean urease, different soils and/or plant-soil systems. The ability of some urease inhibitors to mitigate formation of greenhouse gases is also discussed.

NO, hydrogen sulfide does not come first during tomato response to high salinity.

High salinity greatly impacts agriculture, particularly in tomato (Solanum lycopersicum), a crop that is a model to study this abiotic stress. This work investigated whether hydrogen sulfide (H2S) acts upstream or downstream of nitric oxide (NO) in the signaling cascade during tomato response to salt stress. An NO-donor incremented H2S levels by 12-18.9% while an H2S-donor yielded 10% more NO in roots. The NO accumulated in roots one-hour after NaCl treatment while H2S accumulation started two-hour later. The NO stimulated H2S accumulation in roots/leaves, but not the opposite (i.e H2S was unable to stimulate NO accumulation) two-hour post NaCl treatment. Also, NO accumulation was accompanied by an increment of transcript levels of genes that encode for H2S-synthesizing enzymes. Our results indicate that H2S acts downstream of NO in the mitigation of oxidative stress, which helps tomato plants to tolerate high salinity.

Efficient antibacterial nanosponges based on ZnO nanoparticles and doxycycline.

Bacterial soft rot is responsible for the loss of about 25% of worldwide production in vegetables and fruits. Efforts have been made to develop an effective nanosponge with the capacity to load and release antibacterial drugs to protect plants. Based on the potential of the ZnO nanoparticles (ZnO-NPs) to achieve this goal, this study synthesized NP via the sol-gel and hydrothermal methods by controlling native defects, such as oxygen vacancies, using thermal treatments and reduced atmospheres. To characterize the ZnO NPs, X-ray diffraction (XRD), Raman spectroscopy, transmission electron microscopy (TEM), optical spectroscopy, electron paramagnetic resonance (EPR), Zeta Potential measurements and surface area with the Brunauer-Emmett-Teller (BET) method were used. The photophysical and photochemical properties via spin trapping method aligned with EPR using UVA light showed a greater formation of electron-hole pairs and hydroxyl radicals for the reduced ZnO NPs when compared with the oxidized ones. Additionally, we found that reduced ZnO-NPs have high effectively against Escherichia coli, Erwinia carotovora and Pantoea sp. bacteria using the photocatalytic effect in the UV range. Moreover, ZnO-NPs loaded with DOX release profile enables the release of DOX within 46days, where 25% was released during the first 10h followed by a second delivery phase with an interesting short-term efficacy (<1day) against E. carotovora and Pantoea sp. Bacteria. For the first time, it was demonstrated that ZnO-NPs and ZnO-NPs loaded with DOX have efficient UV photocatalytic activities against bacterial soft rot infections.

Studies on free radical scavenging, cancer cell antiproliferation, and calf thymus DNA interaction of Schiff bases.

Thirty-nine Schiff bases were synthesized by performing microwave-assisted condensation of the corresponding aldehydes and aromatic amines. Their reactive nitrogen species (RNS) scavenging activity and inhibitory effects against cancer cell growth were then subsequently investigated. Additionally, the interaction between the calf thymus DNA (ctDNA) and selected Schiff bases was evaluated using fluorescence spectroscopy, and their binding parameters were determined. The yields of the various compounds ranged from moderate to excellent (43-99%) after only a 2-min reaction. The hydroxylated Schiff bases 2, 8, 15, 16, 18, 20, 29, 32, 34, and 37 were found to be potent scavengers of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals with half-maximal scavenging concentration (SC50) values lower than that of the positive control, resveratrol. The presence of hydroxyl substituents on the aromatic rings also proved essential to the cytotoxicity of the compounds. The binding constants (Kb) obtained using fluorescence spectroscopy ranged from 0.37 to 3.07×105Lmol-1, and were strongly influenced by the structure and hydroxylation degree. Schiff bases 3 and 8 showed promising cytotoxic activity, with half-maximal growth inhibitory (GI50) values in the same order of magnitude as those exhibited by the reference drug, doxorubicin against various cell lines. Interestingly, these compounds also showed the highest Kb, suggesting that the cytotoxic activity could be related to their interaction with the DNA of the tumor cells. The results of this study highlighted some Schiff bases as potential lead compounds for the design of new free radical scavengers and anticancer agents.

Structural Elucidation and Free Radical Scavenging Activity of a new o-Orsellinic Acid Derivative Isolated from the Lichen Cladonia rappii.

Rappiidic acid, a new o-orsellinic acid derivative, was isolated from the lichen Cladonia rappii. Its capability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) was investigated and compared with resveratrol and (+)-usnic acid. Usnic acid at 100 µM was the most efficient ROS scavenger, exhibiting activity 3-fold higher than that of resveratrol. At the same concentration, rappidic acid scavenged 23.1% of ROS formed, demonstrating that this compound is twice as active as resveratrol. Both compounds were shown to be poor RNS scavengers.

A mini-review on Biginelli adducts with notable pharmacological properties.

Since the disclosure of Biginelli reaction by the chemist Pietro Biginelli, functionalized 3,4-dihydropyrimidin-2(1H)-ones/thiones (DHPMs) have emerged as prototypes for the design of compounds with a broad variety of biological activities. This mini-review describes over 100 Biginelli adducts demonstrated to be promising anticancer, inhibitors of calcium channel, anti-inflammatory, antimicrobial and antioxidant agents. Thus, this compilation presents the most notable in vitro and in vivo results for such fascinating class of organic compounds.

An overview on the potential of natural products as ureases inhibitors: A review.

Ureases, enzymes that catalyze urea hydrolysis, have received considerable attention for their impact on living organisms' health and life quality. On the one hand, the persistence of urease activity in human and animal cells can be the cause of some diseases and pathogen infections. On the other hand, food production can be negatively affected by ureases of soil microbiota that, in turn, lead to losses of nitrogenous nutrients in fields supplemented with urea as fertilizer. In this context, nature has proven to be a rich resource of natural products bearing a variety of scaffolds that decrease the ureolytic activity of ureases from different organisms. Therefore, this work compiles the state-of-the-art researches focused on the potential of plant natural products (present in extracts or as pure compounds) as urease inhibitors of clinical and/or agricultural interests. Emphasis is given to ureases of Helicobacter pylori, Canavalia ensiformis and soil microbiota although the active site of this class of hydrolases is conserved among living organisms.

Organ-coordinated response of early post-germination mahogany seedlings to drought.

Water deficit tolerance during post-germination stages is critical for seedling recruitment. In this work, we studied the effect of water deficit on morphological and biochemical responses in different organs of newly germinated mahogany (Swietenia macrophylla King) seedlings, a woody species that occurs in the Amazon rainforest. The root : shoot ratio increased under water deficit. The leaf number and water potential were not altered, although reductions in leaf area and stomatal conductance were observed. Osmotic potential became more negative in leaves of seedlings under severe stress. Water deficit increased fructose, glucose, sucrose and myo-inositol levels in leaves. Stems accumulated fructose, glucose and l-proline. Nitric oxide (NO) levels increased in the vascular cylinder of roots under severe stress while superoxide anion levels decreased due to augmented superoxide dismutase activity in this organ. Water deficit induced glutathione reductase activity in both roots and stems. Upon moderate or severe stress, catalase activity decreased in leaves and remained unaffected in the other seedling organs, allowing for an increase of hydrogen peroxide (H2O2) levels in leaves. Overall, the increase of signaling molecules in distinct organs-NO in roots, l-proline in stems and H2O2 and myo-inositol in leaves-contributed to the response of mahogany seedlings to water deficit by triggering biochemical processes that resulted in the attenuation of oxidative stress and the establishment of osmotic adjustment. Therefore, this body of evidence reveals that the development of newly germinated mahogany seedlings may occur in both natural habitats and crop fields even when water availability is greatly limited.

Introduction to metabolic genetic engineering for the production of valuable secondary metabolites in in vivo and in vitro plant systems.

Plants are capable of producing a myriad of chemical compounds. While these compounds serve specific functions in the plant, many have surprising effects on the human body, often with positive action against diseases. These compounds are often difficult to synthesize ex vivo and require the coordinated and compartmentalized action of enzymes in living organisms. However, the amounts produced in whole plants are often small and restricted to single tissues of the plant or even cellular organelles, making their extraction an expensive process. Since most natural products used in therapeutics are specialized, secondary plant metabolites, we provide here an overview of the classification of the main classes of these compounds, with its biochemical pathways and how this information can be used to create efficient in and ex planta production pipelines to generate highly valuable compounds. Metabolic genetic engineering is introduced in light of physiological and genetic methods to enhance production of high-value plant secondary metabolites.

Biological activities of eco-friendly synthesized Hantzsch adducts.

Fourteen Hantzsch adducts with different substituents at the C-4 position were synthesized through multicomponent reactions by using citric or lactic acid as catalysts. To the best of our knowledge, this is the first report on the synthesis of such a class of compounds based on multicomponent reactions catalyzed by non-toxic organic acids. The potential to scavenge reactive nitrogen/oxygen species (RNS/ROS) and the ability to inhibit cancer cell growth were then investigated. Among the synthesized compounds, adduct 15 was the most promising free radical scavenger, while adduct 20 was shown to have a wider spectrum of action on the cancer cells studied. These results highlight Hantzsch adducts as lead compounds for obtaining new free radical scavengers and anticancer agents.

Design of new drugs for the treatment of Alzheimer's disease based on tacrine structure.

Tacrine was the first drug approved by FDA for the treatment of Alzheimer's disease. However, its use was restricted in function of side effects observed in some patients. Investigations on the structural basis by which tacrine inhibits cholinesterases activity brought new perspectives for the design of more potent analogs with fewer side effects. This review discusses the recent advances on the development of tacrine-structure-based compounds capable to target multiple molecules involved in Alzheimer's disease. Detailed information on strategies of molecular modifications commonly used in medicinal chemistry, such as bioisosterism, hybridization, dimerization and simplification is presented as well.