Electric generators are largely employed as emergency power sources by preventing some facilities from sudden interruptions of electric energy supply. They may also be used to reduce the energy ...demand from the power grid by providing electricity over the peak periods. This paper aims to evaluate the owners' economic risk of purchasing an electric generator in order to provide energy during the peak time. The study considers different rated powers of diesel and natural gas-based generators as well as cases with and without an extra expense due to the carbon credit (CCr), which is a cost generated by the emission of greenhouse gases (GHG). Net Present Value (NPV) is used as a method for the economic feasibility analysis while Monte Carlo Simulation (MCS), a stochastic approach, is performed to evaluate the economic risk. To verify the applied methodology and accomplish the goals of this work, a Brazilian university project is taken as a case study and the campus is assumed to be an investor of an electric generator. The analysis is performed considering that the facilities are fed energetically during short periods of the day. All rules from Brazilian energy market are taken into consideration. Diesel and natural gas-based generators are able to guarantee a low risk of return on investment to investors and such risk is truly dependent on the generator rated power. Diesel generators present a narrow range of rated powers with a high probability of positive NPV whereas natural gas-based engines show a wide range of them with a null risk of an unprofitable purchase. In cases where carbon credits are considered as extra costs, the probability of a failed business is always higher than the cases they are not taken into account, although the carbon credits have no high sensitivity in the risk analysis.
•Diesel and natural gas-based generators' projects evaluated economically.•Both diesel and natural gas-based generators are cost-effective.•The generators' rated power highly influence the economic risk of the project.•A profitable business depends on ranges of rated power values.•The carbon credit has not a significant impact to the risk analysis.
•A pure wind system is the economically ideal configuration.•The likelihood of positive NPV decreases as more PV power is inserted.•The more PV arrays are installed, the less feasible becomes the ...business.•PV systems still require high investment costs compared to wind complexes.•PV systems have a low cf in comparison with wind systems.
In order to mitigate the lack of energy production, several types of energy sources have been combined in a so-called hybrid energy system; however, some economic analysis must be performed to evaluate whether the hybrid business is financially feasible. This work aims to evaluate wind-PV hybrid systems technical and economically through the simulation of a hypothetical hybrid power plant in which a case study is presented. The economic viability of PV power into wind systems is assessed by the comparison of distinct scenarios, which consider different rated power for each type of source. The paper regards the context of the Brazilian energy market and is geared toward the rules, the current tariff prices, and the mean investment applied for the construction of wind and PV systems in Brazil nowadays. The results show that a pure wind energy system is economically ideal and the continuous insertion of PV power into the wind system decreases the chances of profitability. However, for certain amount of PV rated power installed in the complex, the project maintains a high probability of being successful.
Alzheimer’s disease (AD) is a neurodegenerative disorder caused by accumulation of amyloid-β oligomers (AβO) in the brain, neuroinflammation, oxidative stress, and cognitive decline. Grandisin, a ...tetrahydrofuran neolignan, exhibits relevant anti-inflammatory and antioxidant properties. Interestingly, grandisin-based compounds were shown to prevent AβO-induced neuronal death in vitro. However, no study has assessed the effect of these compounds on the AD animal model. This study focuses on a triazole grandisin analogue (TGA) synthesized using simplification and bioisosteric drug design, which resulted in improved potency and solubility compared with the parent compound. This study aimed to investigate the possible in vivo effects of TGA against AβO-induced AD. Male C57/Bl6 mice underwent stereotaxic intracerebroventricular AβO (90 μM) or vehicle injections. 24 h after surgery, animals received intraperitoneal treatment with TGA (1 mg/kg) or vehicle, administered on a 14 day schedule. One day after treatment completion, a novel object recognition task (NORT) was performed. Memantine (10 mg/kg) was administered as a positive control. NORT retention sessions were performed on days 8 and 16 after AβO injection. Immediately after retention sessions, animals were euthanized for cortex and hippocampus collection. Specimens were subjected to oxidative stress and cytokine analyses. TGA reduced the level of cortex/hippocampus lipoperoxidation and prevented cognitive impairment in AβO-injected mice. Additionally, TGA reduced tumor necrosis factor (TNF) and interferon-γ (IFN-γ) levels in the hippocampus. By contrast, memantine failed to prevent cortex/hippocampus lipid peroxidation, recognition memory decline, and AβO-induced increases in TNF and IFN-γ levels in the hippocampus. Thus, memantine was unable to avoid the AβO-induced persistent cognitive impairment. The results showed that TGA may prevent memory impairment by exerting antioxidant and anti-inflammatory effects in AβO-injected mice. Moreover, TGA exhibited a persistent neuroprotective effect compared to memantine, reflecting an innovative profile of this promising agent against neurodegenerative diseases, such as AD.
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•Synthesis of novel 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids.•Non-ulcerogenic in animal model.•Possible double inhibition of COX-2 and 5-LOX.•Comparable molecular docking ...of celecoxib and analogs.•Novel neolignan-celecoxib hybrids decreased the expression of P-selectin (CD62P)•Distinct butterfly-shaped hybrid analogs may indicate lower levels of thrombogenic events compared to the coxibs.
This study reports the synthesis of novel neolignans-celecoxib hybrids and the evaluation of their biological activity. Analogs8–13(L13-L18) exhibited anti-inflammatory activity, inhibited glycoprotein expression (P-selectin) related to platelet activation, and were considered non– ulcerogenic in the animal model, even with the administration of 10 times higher than the dose used in reference therapy. In silico drug-likeness showed that the analogs are compliant with Lipinski’s rule of five. A molecular docking study showed that the hybrids8–13(L13-L18) fitted similarly with celecoxib in the COX-2 active site. According to this data, it is possible to infer that extra hydrophobic interactions and the hydrogen interactions with the triazole core may improve the selectivity towards the COX-2 active site. Furthermore, the molecular docking study with P-selectin showed the binding affinity of the analogs in the active site, performing important interactions with amino acid residues such as Tyr 48. Whereas the P-selectin is a promising target to the design of new anti-inflammatory drugs with antithrombotic properties, a distinct butterfly-like structure of 1,4-diaryl-1,2,3-triazole neolignan-celecoxib hybrids synthesized in this work may be a safer alternative to the traditional COX-2 inhibitors.
Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis ...intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.
The spatial variability of physical properties, such as bulk density, penetration resistance and gravimetric moisture, obtained by applying geostatistics in precision agriculture, can effectively ...indicate the physical behavior of agricultural soils in longitudinal profiles. In this way, the spatial dependence of physical properties in streets of coffee plantations with different lengths was evaluated in the southern Minas Gerais, Brazil. For this purpose, five longitudinal profiles were measured in streets, each one with depths ranging from 0 to 0.60 m, in six layers of 0.10 m, being the database composed of 432 property, 144 by property, submitted to the ordinary kriging geostatistical method in order to obtain spatial variability maps using the R software. They were evaluated by the lower mean cross-validation error of theoretical models fitted by ordinary least squares (OLS), being detected in higher superficial layers, from 0 to 0.30 m, lower bulk density and lower penetration resistance, with variable gravimetric moisture in the length direction of some streets of coffee plantations, being that these properties presented different structures of spatial dependence for each street.
A series of 28 compounds, 3-nitro-1H-1,2,4-triazole, were synthesized by click-chemistry with diverse substitution patterns using medicinal chemistry approaches, such as bioisosterism, Craig-plot, ...and the Topliss set with excellent yields. Overall, the analogs demonstrated relevant in vitro antitrypanosomatid activity. Analog 15g (R1 = 4-OCF3–Ph, IC50 = 0.09 μM, SI = >555.5) exhibited an outstanding antichagasic activity (Trypanosoma cruzi, Tulahuen LacZ strain) 68-fold more active than benznidazole (BZN, IC50 = 6.15 μM, SI = >8.13) with relevant selectivity index, and suitable LipE = 5.31. 15g was considered an appropriate substrate for the type I nitro reductases (TcNTR I), contributing to a likely potential mechanism of action for antichagasic activity. Finally, 15g showed nonmutagenic potential against Salmonella typhimurium strains (TA98, TA100, and TA102). Therefore, 3-nitro-1H-1,2,4-triazole 15g is a promising antitrypanosomatid candidate for in vivo studies.
Chagas disease and leishmaniasis are neglected diseases of high priority as a public health problem. Pharmacotherapy is based on the administration of a few drugs, which exhibit hazardous adverse ...effects and toxicity to the patients. Thus, the search for new antitrypanosomatid drugs is imperative to overcome the limitations of the treatments. In this work, 46 2-nitroimidazole 3,5-disubstituted isoxazole compounds were synthesized in good yields by 3 + 2 cycloaddition reaction between terminal acetylene (propargyl-2-nitroimidazole) and chloro-oximes. The compounds were non-toxic to LLC-MK2 cells. Compounds 30, 35, and 44 showed in vitro antichagasic activity, 15-fold, 12-fold, and 10-fold, respectively, more active than benznidazole (BZN). Compounds 30, 35, 44, 45, 53, and 61 acted as substrates for the TcNTR enzyme, indicating that this might be one of the mechanisms of action involved in their antiparasitic activity. Piperazine series and 4-monosubstituted compounds were potent against T. cruzi parasites. Besides the in vitro activity observed in compound 45, the in vivo assay showed that the compound only reduced the parasitemia levels by the seventh-day post-infection (77%, p > 0.001) compared to the control group. However, 45 significantly reduced the parasite load in cardiac tissue (p < 0.01) 11 days post-infection. Compounds 49, 52, and 54 showed antileishmanial activity against intracellular amastigotes of Leishmania (L.) amazonensis at the same range as amphotericin B. These findings highlight the antitrypanosomatid properties of 2-nitroimidazole 3,5-disubstituted isoxazole compounds and the possibility in using them as antitrypanosomatid agents in further studies.
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•46 novel 2-nitroimidazole-3,5-isoxazole-based derivatives of benznidazole (BZN) have been synthesized.•Isoxazole-piperazine series were active against T. cruzi and L. amazonensis.•Several compounds showed in vitro antichagasic activity and four of them exhibited activity <1 μM.•Correlation of a threshold value of optimal lipophilicity and antichagasic potency in piperazine series.•Electron-donating substituents in position 4 provided potent monosubstituted compounds against T. cruzi parasites.•In vivo study with compound 45 (25 mg/kg/day) promoted the reduction of parasite load in cardiac tissue.•Type I nitroreductases (TcNTR) might be one of the action mechanisms involved in their antiparasitic activity.•The in vitro antileishmanial assay (L. amazonensis) showed that different compounds were more active than the reference drugs tested as a control.
A series of 28 compounds, 3-nitro-1
-1,2,4-triazole, were synthesized by click-chemistry with diverse substitution patterns using medicinal chemistry approaches, such as bioisosterism, Craig-plot, ...and the Topliss set with excellent yields. Overall, the analogs demonstrated relevant in vitro antitrypanosomatid activity. Analog
(R
= 4-OCF
-Ph, IC
= 0.09 μM, SI = >555.5) exhibited an outstanding antichagasic activity (
, Tulahuen LacZ strain) 68-fold more active than benznidazole (BZN, IC
= 6.15 μM, SI = >8.13) with relevant selectivity index, and suitable LipE = 5.31.
was considered an appropriate substrate for the type I nitro reductases (TcNTR I), contributing to a likely potential mechanism of action for antichagasic activity. Finally,
showed nonmutagenic potential against
strains (TA98, TA100, and TA102). Therefore, 3-nitro-1
-1,2,4-triazole
is a promising antitrypanosomatid candidate for in vivo studies.
Despite some advantages, renewable sources pose certain financial risks for investors in the industry. These risks are mainly associated with the oscillation of energy production, the prices and ...rules of the energy market, and the possibility of delays and anticipations at the conclusion of works. In order to mitigate the likelihood of low power production, distinct sorts of power sources have been combined into one integrated system so that you may take advantage of source complementarity and network asset sharing. This work studies the financial risk associated with the anticipation or delay in the completion of projects in the Brazilian energy market considering the insertion of photovoltaic sources in an integrated wind-solar power plant. To evaluate the project feasibility, Net Present Value is used as deterministic method and Monte Carlo Simulation is performed as stochastic valuation model through some historical data obtained. The economic risk assessment showed that delayed works significantly increase the probability of a failed business regardless of the proportion of the sources in the integrated system. Projects finished earlier, in contrast, increase the chances of a profitable business, although this increase is less significant in systems with lower installed photovoltaic source and more relevant to systems with a higher proportion of integrated solar source.
•Delayed works sharply reduce the likelihood of a protable business for any scenario•Works concluded in advance contribute to a thriving undertaking•Works concluded in advance are more signicant for certain scenarios•The likelihood of positive NPV drops as PV power is inserted into the system
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