In this communication, lipase A from
(CALA) was immobilized by covalent bonding on magnetic nanoparticles coated with chitosan and activated with glutaraldehyde, labelled CALA-MNP, (immobilization ...parameters: 84.1% ± 1.0 for immobilization yield and 208.0 ± 3.0 U/g ± 1.1 for derivative activity). CALA-MNP biocatalyst was characterized by X-ray Powder Diffraction (XRPD), Fourier Transform Infrared (FTIR) spectroscopy, Thermogravimetry (TG) and Scanning Electron Microscope (SEM), proving the incorporation of magnetite and the immobilization of CALA in the chitosan matrix. Besides, the immobilized biocatalyst showed a half-life 8-11 times higher than that of the soluble enzyme at pH 5-9. CALA showed the highest activity at pH 7, while CALA-MNP presented the highest activity at pH 10. The immobilized enzyme was more active than the free enzyme at all studied pH values, except pH 7.
Adenosine Receptor Type 2A (A
AR) plays a role in important processes, such as anti-inflammatory ones. In this way, the present work aimed to search for compounds by pharmacophore-based virtual ...screening. The pharmacokinetic/toxicological profiles of the compounds, as well as a robust QSAR, predicted the binding modes via molecular docking. Finally, we used molecular dynamics to investigate the stability of interactions from ligand-A
AR. For the search for A
AR agonists, the UK-432097 and a set of 20 compounds available in the BindingDB database were studied. These compounds were used to generate pharmacophore models. Molecular properties were used for construction of the QSAR model by multiple linear regression for the prediction of biological activity. The best pharmacophore model was used by searching for commercial compounds in databases and the resulting compounds from the pharmacophore-based virtual screening were applied to the QSAR. Two compounds had promising activity due to their satisfactory pharmacokinetic/toxicological profiles and predictions via QSAR (Diverset 10002403 pEC
= 7.54407; ZINC04257548 pEC
= 7.38310). Moreover, they had satisfactory docking and molecular dynamics results compared to those obtained for Regadenoson (Lexiscan
), used as the positive control. These compounds can be used in biological assays (in vitro and in vivo) in order to confirm the potential activity agonist to A
AR.
In this work, a nanohybrid material was developed and used for the first time to the kinetic resolution of secondary alcohols as
rac
-indanol,
rac
-1-phenylethanol (
rac
-1),
rac
...-1-(3-bromophenyl)-1-ethanol (
rac
-2) and
rac
-1-(3-methylphenyl)-1-ethanol (
rac
-3). Chiral indanol is used as a precursor intermediate for the synthesis of enantiomeric drugs, such as (+)-Indatraline, Irindalone, Indinavir, (+)-Sertraline and Rasagiline mesylate. Chiral 1-phenylethanol is used as an ophthalmic preservative, a solvatochromic dye and an inhibitor of cholesterol absorption and as a mild floral fragrance. For this purpose, the ultrasound irradiation was used to couple APTES on the superparamagnetic nanoparticles surface. Then, the system was activated with glutaraldehyde and used as a support for immobilization of lipase from
Pseudomonas fluorescens.
Thermal stability analysis was performed in buffer and hexane, showing an excellent stability in buffer solution at 60 °C, holding 72% of the initial activity, even after 7 h. In hexane (40 °C), the immobilized enzyme retained 100% of activity with 693 min of half-life time at 50 °C. The high thermal stability is mainly related to the covalent bonding between enzymes and support. Immobilized lipase on magnetic support proved to be a robust biocatalyst in the kinetic resolution, leading to (
S
)-indanol with high selectivity (
e.e
. > 99%,
E
> 200) in 1.75 h at 50 °C, being reused five times without significant loss of the activity and selectivity. The kinetic resolution of
rac
-1, via acetylation reaction, catalyzed by lipase from
Pseudomonas fluorescens
immobilized on magnetic support, led to (
R
)-acetate with enantiomeric excess > 99% and to the remaining (
S
)-alcohol with enantiomeric excess of 94%, conversion of 49% and
E
> 200, after 48 h of reaction at 40 °C. Under the same reactions conditions,
ra
c-2 and
rac
-3 were slightly less reactive, since the corresponding (
R
)-acetates were obtained with conversion values of 44%, but with high enantioselectivity (enantiomeric excesses > 99% and
E
values > 200). These results correspond to an important step in heterogeneous catalysis due to the ability to obtain important precursors for the synthesis of enantiomerically pure chiral drugs and other bioactive substances.
The synthesis of ethyl butyrate catalyzed by lipases A (CALA) or B (CALB) from
immobilized onto magnetic nanoparticles (MNP), CALA-MNP and CALB-MNP, respectively, is hereby reported. MNPs were ...prepared by co-precipitation, functionalized with 3-aminopropyltriethoxysilane, activated with glutaraldehyde, and then used as support to immobilize either CALA or CALB (immobilization yield: 100 ± 1.2% and 57.6 ± 3.8%; biocatalysts activities: 198.3 ± 2.7 U
/g and 52.9 ± 1.7 U
/g for CALA-MNP and CALB-MNP, respectively). X-ray diffraction and Raman spectroscopy analysis indicated the production of a magnetic nanomaterial with a diameter of 13.0 nm, whereas Fourier-transform infrared spectroscopy indicated functionalization, activation and enzyme immobilization. To determine the optimum conditions for the synthesis, a four-variable Central Composite Design (CCD) (biocatalyst content, molar ratio, temperature and time) was performed. Under optimized conditions (1:1, 45 °C and 6 h), it was possible to achieve 99.2 ± 0.3% of conversion for CALA-MNP (10 mg) and 97.5 ± 0.8% for CALB-MNP (12.5 mg), which retained approximately 80% of their activity after 10 consecutive cycles of esterification. Under ultrasonic irradiation, similar conversions were achieved but at 4 h of incubation, demonstrating the efficiency of ultrasound technology in the enzymatic synthesis of esters.
The
genus comprises opportunistic fungi that can become pathogenic when the immune system of the host fails.
is the most important and prevalent species. Polyenes, fluoropyrimidines, echinocandins, ...and azoles are used as commercial antifungal agents to treat candidiasis. However, the presence of intrinsic and developed resistance against azole antifungals has been extensively documented among several
species. The advent of original and re-emergence of classical fungal diseases have occurred as a consequence of the development of the antifungal resistance phenomenon. In this way, the development of new satisfactory therapy for fungal diseases persists as a major challenge of present-day medicine. The design of original drugs from traditional medicines provides new promises in the modern clinic. The urgent need includes the development of alternative drugs that are more efficient and tolerant than those traditional already in use. The identification of new substances with potential antifungal effect at low concentrations or in combination is also a possibility. The present review briefly examines the infections caused by
species and focuses on the mechanisms of action associated with the traditional agents used to treat those infections, as well as the current understanding of the molecular basis of resistance development in these fungal species. In addition, this review describes some of the promising alternative molecules and/or substances that could be used as anticandidal agents, their mechanisms of action, and their use in combination with traditional drugs.
Lipase from
Rhizomucor miehei
(RML) was immobilized onto chitosan support in the presence of some surfactants added at low levels using two different strategies. In the first approach, the enzyme was ...immobilized in the presence of surfactants on chitosan supports previously functionalized with glutaraldehyde. In the second one, after prior enzyme adsorption on chitosan beads in the presence of surfactants, the complex chitosan beads-enzyme was then cross-linked with glutaraldehyde. The effects of surfactant concentrations on the activities of free and immobilized RML were evaluated. Hexadecyltrimethylammonium bromide (CTAB) promoted an inhibition of enzyme activity while the nonionic surfactant Triton X-100 caused a slight increase in the catalytic activity of the free enzyme and the derivatives produced in both methods of immobilization. The best derivatives were achieved when the lipase was firstly adsorbed on chitosan beads at 4 °C for 1 h, 220 rpm followed by cross-link the complex chitosan beads-enzyme with glutaraldehyde 0.6% v.v
−1
at pH 7. The derivatives obtained under these conditions showed high catalytic activity and excellent thermal stability at 60° and 37 °C. The best derivative was also evaluated in the synthesis of two flavor esters namely methyl and ethyl butyrate. At non-optimized conditions, the maximum conversion yield for methyl butyrate was 89%, and for ethyl butyrate, the esterification yield was 92%. The results for both esterifications were similar to those obtained when the commercial enzyme Lipozyme® and free enzyme were used in the same reaction conditions and higher than the one achieved in the absence of the selected surfactant.
The guidelines for the Environmental Risk Assessment (ERA) of pharmaceuticals and personal care products (PPCP) recommend the use of standard ecotoxicity assays and the assessment of endpoints at the ...individual level to evaluate potential effects of PPCP on biota. However, effects at the sub-individual level can also affect the ecological fitness of marine organisms chronically exposed to PPCP. The aim of the current study was to evaluate the environmental risk of two PPCP in marine sediments: triclosan (TCS) and ibuprofen (IBU), using sub-individual and developmental endpoints. The environmental levels of TCS and IBU were quantified in marine sediments from the vicinities of the Santos submarine sewage outfall (Santos Bay, São Paulo, Brazil) at 15.14 and 49.0 ng g−1, respectively. A battery (n = 3) of chronic bioassays (embryo-larval development) with a sea urchin (Lytechinus variegatus) and a bivalve (Perna perna) were performed using two exposure conditions: sediment-water interface and elutriates. Moreover, physiological stress through the Neutral Red Retention Time Assay (NRRT) was assessed in the estuarine bivalve Mytella charruana exposed to TCS and IBU spiked sediments. These compounds affected the development of L. variegatus and P. perna (75 ng g−1 for TCS and 15 ng g−1 for IBU), and caused a significant decrease in M. charruana lysosomal membrane stability at environmentally relevant concentrations (0.08 ng g−1 for TCS and 0.15 ng g−1 for IBU). Chemical and ecotoxicological data were integrated and the risk quotient estimated for TCS and IBU were higher than 1.0, indicating a high environmental risk of these compounds in sediments. These are the first data of sediment risk assessment of pharmaceuticals and personal care products of Latin America. In addition, the results suggest that the ERA based only on individual-level and standard toxicity tests may overlook other biological effects that can affect the health of marine organisms exposed to PPCP.
Display omitted
•Triclosan and ibuprofen were quantified in order of ng.g-1 in marine sediment.•Adverse effects were found in environmentally relevant concentrations.•Mytella charruana is an alternative species for monitoring marine and estuarine sediments.•Significant environmental risk for triclosan and ibuprofen in a tropical coastal zone.
This study presents the first data of sediment risk assessment of pharmaceuticals and personal care products in Latin America.
Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of ...species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.
Patients with ischemic heart failure (iHF) have a high risk of neurological complications such as cognitive impairment and stroke. We hypothesized that iHF patients have a higher incidence of ...impaired dynamic cerebral autoregulation (dCA). Adult patients with iHF and healthy volunteers were included. Cerebral blood flow velocity (CBFV, transcranial Doppler, middle cerebral artery), end-tidal CO
(capnography), and arterial blood pressure (Finometer) were continuously recorded supine for 5 min at rest. Autoregulation index (ARI) was estimated from the CBFV step response derived by transfer function analysis using standard template curves. Fifty-two iHF patients and 54 age-, gender-, and BP-matched healthy volunteers were studied. Echocardiogram ejection fraction was 40 (20-45) % in iHF group. iHF patients compared with control subjects had reduced end-tidal CO
(34.1 ± 3.7 vs. 38.3 ± 4.0 mmHg, P < 0.001) and lower ARI values (5.1 ± 1.6 vs. 5.9 ± 1.0, P = 0.012). ARI <4, suggestive of impaired CA, was more common in iHF patients (28.8 vs. 7.4%, P = 0.004). These results confirm that iHF patients are more likely to have impaired dCA compared with age-matched controls. The relationship between impaired dCA and neurological complications in iHF patients deserves further investigation.
Green hydrogen production is expected to have a major contribution in addressing the global challenge of energy transition and economy decarbonization. In such a transition, wind energy is considered ...as one of the principal electricity sources for H2 production, both because it is a sustainable source and owing to the intermittency of the wind resource. In recent years, new wind farms have gradually moved offshore, due to better wind resource quality and due to limited space onshore. However, a mismatch between instantaneous wind energy availability and electricity demand often leads to wasting some of the wind resource, usually referred to as curtailment events. Such an excess energy could be used to produce hydrogen and thus make efficient and integrated use of the available equipment and resources. The present work analyzes the feasibility of hydrogen production employing electricity generated from wind energy, taking the WindFloat Atlantic offshore wind farm and Portugal’s electricity market as a case-study.
Two scenarios are considered. Scenario 1 assumes the WindFloat Atlantic wind farm’s present capacity of 25.2 MW and scenario 2 considers a long-term commercial phase of 150 MW integrated in a developed hydrogen economy with pipelines for H2 distribution. In both scenarios a readily available PEM electrolyzer system is employed and the benefits of complementary oxygen sales are estimated. The availability of the wind resource and occurrence of different wind conditions for the particular location is estimated from the wind energy atlas. Afterwards, correlations between the renewable energy production and wholesale electricity price in the Iberian market are established by processing the data corresponding to the year 2019 and taking seasonal variations into account.
For each of scenarios, two cases are considered. Case A assumes hydrogen is produced only at night whereas Case B allows for production both during nights and afternoons. Results show Case B and oxygen sales contribute to a more economically feasible project. For Case B and assuming a H2 selling price of 8 €/kg, discount rate (10%) and corporate tax of 21%, results show scenario 2 is the only profitable solution, due to the long-term lower costs. Scenario 1 appears to be feasible only with government incentives. The ratio between the hydrogen plant power and wind farm capacity (PPR) has a significant impact on the H2 production, with results showing a minimum in H2 cost for a ratio of approximately 30%.
•Feasibility of H2 production using electricity from a Portuguese offshore wind farm.•Dynamic power curve for the IEA-15 MW wind turbine in a semi-submersible platform.•Electricity prices vs. wind production obtained from a 2019 MIBEL market’s analysis.•Consideration of PEM technology, H2 compression, and O2 liquification storage.•LCOH may reach 4.65 €/kg when produced during nights and afternoons, in the long-term scenario.
PDF
