The Cyclodextrins as Modelling Agents of Drug Controlled Release

The controlled release of nicardipine (NC) was achieved by hybridizing its hydrophilic and hydrophobic cyclodextrin (CDs) complexes, i.e., those with hydroxypropyl-ß-cyclodextrin (HPßCD) andtriacetyl-ß-cyclodextrin (TAßCD),respectively. 1H-nuclearmagnetic resonance (1H-NMR) was performed to examine the interaction between both CDs and NC in solution. The solid complexes of NC : HPßCD and NC : TAßCD were prepared, in a 1 : 1 molar ratio by the spray-drying method. Complexation in the solid state was demonstrated by differential scanning calorimetry (DSC) and powder X-ray diffractometry. In vitro dissolution studies were carried out in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the USP basket method. The 1H-NMR studies provided clear evidence of an interaction between the CDs and the aromatic rings of NC. The DSC thermograms of the solid complexes showed no endothermic peak due to NC melting and their diffraction pattern was completely diffuse, which suggested the formation of a novel type solid phase with an amorphous character. The low dissolution rate of NC, a weak basic drug, in alkaline medium was significantly improved by complexation with HPßCD. In contrast, the in vitro release of this drug from the NC : TAßCD complexes was markedly retarded in both dissolution media. An optimal formulation was then designed by the combination, in different molar ratios, of these two complexes. The release behavior of these preparations was investigated and it was observed that the retarding effect was dependent on the amount of the NC : TAßCD complex. In addition, the initial release rate became faster as the molar ratio of the NC : HPßCD complex increased

On hair care physicochemistry: From structure and degradation to novel biobased conditioning agents

Hair is constantly exposed to various adverse external stimuli, such as mechanical or thermal factors, that may cause damage or cause it to lose its shine and smooth appearance. These undesirable effects can be minimized by using hair conditioners, which repair the hair and restore the smooth effect desired by the consumer. Some of the currently used conditioning agents present low biodegradability and high toxicity to aquatic organisms. Consumers are also becoming more aware of environmental issues and shifting their preferences toward natural-based products. Therefore, developing novel, sustainable, natural-based derivatives that can act as conditioning agents in hair care products and thus compete with the traditional systems obtained from non-renewable sources is highly appealing. This paper presents the key physicochemical aspects of the hair conditioning process, including hair structure and degradation, and reviews some of the new alternative conditioning agents obtained from natural resources.info:eu-repo/semantics/publishedVersio

Structure, dynamics, and stability of the globular domain of human linker histone H1.0 and the role of positive charges

Linker histone H1 (H1) is an abundant chromatin-binding protein that acts as an epigenetic regulator binding to nucleosomes and altering chromatin structures and dynamics. Nonetheless, the mechanistic details of its function remain poorly understood. Recent work suggest that the number and position of charged side chains on the globular domain (GD) of H1 influence chromatin structure and hence gene repression. Here, we solved the solution structure of the unbound GD of human H1.0, revealing that the structure is almost completely unperturbed by complex formation, except for a loop connecting two antiparallel β-strands. We further quantified the role of the many positive charges of the GD for its structure and conformational stability through the analysis of 11 charge variants. We find that modulating the number of charges has little effect on the structure, but the stability is affected, resulting in a difference in melting temperature of 26 K between GD of net charge +5 versus +13. This result suggests that the large number of positive charges on H1-GDs have evolved for function rather than structure and high stability. The stabilization of the GD upon binding to DNA can thus be expected to have a pronounced electrostatic component, a contribution that is amenable to modulation by posttranslational modifications, especially acetylation and phosphorylation. Keywords: CD; NMR; histone; nucleosome; protein electrostatics; protein stability; protein structur

Exploring the biotechnological value of marine invertebrates: a closer look at the biochemical and antioxidant properties of Sabella spallanzanii and Microcosmus squamiger

Sabella spallanzanii and Microcosmus squamiger were profiled for proximate composition, minerals, amino acids, fatty acids (FA), carotenoids, radical scavenging activity on the 2,2-diphenyl-1- picrylhydrazyl (DPPH) radical, oxygen radical absorbance capacity (ORAC) and iron and copper chelating properties. Microcosmus squamiger had the highest level of moisture and crude protein, S. spallanzanii was enriched in crude fat and ash. Both species had similar levels of carbohydrates and energy. There was a prevalence of arginine and glycine in S. spallanzanii, and of taurine in M. squamiger. The most abundant minerals in both species were Na, Ca, and K. The methanol extract of S. spallanzanii had metal chelating properties towards copper and iron, while the methanol extract of M. squamiger was able to chelate copper. M. squamiger extracts had similar ORAC values. Fucoxanthinol and fucoxanthin were the major carotenoids in the M. squamiger dichloromethane extract. Saturated FA were more abundant than unsaturated ones in methanol extracts, and unsaturated FA prevailed in the dichloromethane extracts. Palmitic acid was the predominant FA in methanol extracts, whereas eicosapentaenoic (EPA) and dihomo-γ-linolenic acids were the major compounds in dichloromethane extracts. Low n-6/n-3 ratios were obtained. Our results suggests that both species could be explored as sources of bioactive ingredients with multiple applications.info:eu-repo/semantics/publishedVersio

synthesis of cernumidine and analogues, and survey of its anti-inflammatory activity

C. S. B. Gomes acknowledges the XTAL – Macromolecular Crystallography group (UCIBIO and i4HB) for granting access to the X-ray diffractometer. X-Ray infrastructure was financed by FCT-MCTES through project RECI/BBBBEP/0124/2012. Publisher Copyright: © 2024 The Royal Society of Chemistry.A novel approach has been developed for the efficient synthesis of the unsymmetrical (2-aminopyrrolidin-1-yl)carboxamidine alkaloidal core found in cernumidine (1) and its analogs (20a, 20c, 20f, 20i-o). The key transformation in this process involves the utilization of the Curtius rearrangement, which plays a pivotal role in constructing the aminal moiety. One of the major challenges encountered during this synthesis was the instability of the free aminal core intermediate. Furthermore, a noteworthy observation during the synthesis was the racemization process that occurred during the isocyanate trapping by organometallic reagents. Detailed DFT calculations shed light on this phenomenon, revealing a neighboring coordination-induced mechanism. The resulting compounds were subjected to evaluation for their anti-inflammatory properties using lipopolysaccharide-stimulated human THP1 cells. Notably, compounds featuring the guanidine moiety and electron-donating groups exhibited significant anti-inflammatory activity. These findings suggest that these compounds hold promise as potential candidates for further development as anti-inflammatory agents.publishersversionpublishe

Eugenol β-amino/β-alkoxy alcohols with selective anticancer activity

Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol β-amino alcohol and β-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three β-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.This research was funded by FCT under project PTDC/ASP-AGR/30154/2017 (PO-CI-01-0145- FEDER-030154) of COMPETE 2020, co-financed by FEDER and EU. FCT-Portugal and FEDERCOMPETE/ QREN-EU also gave financial support to the research centres CQ/UM (UIDB/00686/2020) and REQUIMTE (UIDB/50006/2020). The NMR spectrometer Bruker Avance III 400 (part of the National NMR Network) was financed by FCT and FEDER. Renato B. Pereira acknowledges PRIMA Foundation (H2020- PRIMA 2018—Section 2, Project MILKQUA) and FCT (PTDC/QUI-QFI/2870/2020) for the funding

Cysteine as a Multifaceted Player in Kidney, the Cysteine-Related Thiolome and Its Implications for Precision Medicine

Funding Information: This research was supported by Fundação para a Ciência e Tecnologia (PTDC/MED-TOX/30418/2017) and iNOVA4Health (UID/Multi/04462/2013). M.J.C., D.G.F.F. and J.M. were supported by FCT (PhD grant SFRH/BD/131331/2017, PhD grant PD/BD/135484/2018 and postdoctoral contract PTDC/MED-TOX/30418/2017, respectively).In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine.publishersversionpublishe

Plant aqueous extracts: antioxidant capacity via haemolysis and bacteriophage P22 protection

The bacteriophage P22/Salmonella Typhimurium system, as well as human erythrocytes have been used to assay for protection, against forced oxidation caused by hydrogen peroxide, brought about by several aqueous extracts of selected adventitious plants grown in Portugal. This study proved, for the first time, that the aforementioned bacteriophage-based system is a suitable method to assess the antioxidant activity of plant extracts; among the 12 plants tested, raspberry (Rubus idaeus), sage (Salvia sp.), savory (Satureja montana) and yarrow (Achillea millefolium) were found to effectively protect against oxidative damage caused by H2O2. Haemolysis was inhibited via pre-treatment with every plant extract tested, except heath at 0.1% (w/v). The two analytical methods produced different results – and for some plants, there was a dependence (either direct or inverse) of the quantitative protection effect on extract concentration, whereas for others no significant dependence was found at all. Savory yielded the most promising results, using either method. Therefore, the P22/Salmonella system can be used as a suitable in vivo assay, and human erythrocytes as a suitable in vitro assay to confirm (or not) the antioxidant capacity of plant extracts in biological matrices.info:eu-repo/semantics/acceptedVersio