Publications

Abstract Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin (endo coumarin-resveratrol-inspired hybrid) and trans-6-styrylcoumarin (exo coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with trans-6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than trans-resveratrol.

Abstract A new sensing platform based on long-period fiber gratings (LPFGs) for direct, fast, and selective detection of human immunoglobulin G (IgG; Mw = 150 KDa) was developed and characterized. The transducer's high selectivity is based on the specific interaction of a molecularly imprinted polymer (MIPs) design for IgG detection. The sensing scheme is based on differential refractometric measurements, including a correction system based on a non-imprinted polymer (NIP)-coated LPFG, allowing reliable and more sensitive measurements, improving the rejection of false positives in around 30%. The molecular imprinted binding sites were performed on the surface of a LPFG with a sensitivity of about 130 nm/RIU and a FOM of 16 RIU-1. The low-cost and easy to build device was tested in a working range from 1 to 100 nmol/L, revealing a limit of detection (LOD) and a sensitivity of 0.25 nmol/L (0.037 mu g/mL) and 0.057 nm.L/nmol, respectively. The sensor also successfully differentiates the target analyte from the other abundant elements that are present in the human blood plasma.

Abstract In this work, the stability of antioxidant compounds in malting barley seeds before and after the production of the final products is reported. In this reflection, the findings revealed that the process of fermentation had a significant impact on antioxidant activity. In vitro, antioxidant capacities were evaluated using DPPH free radical scavenging assay. The results obtained from the spectrophotometric analysis showed that the lowest inhibition value was observed in the samples that were obtained by the classical fermentation process (ABC) and the samples of non-alcoholic beer obtained by the thermal process (NABT), with free radical inhibition capacity values of 8.50% and 5.50%, respectively. The samples of hopped wort (HW) and malted barley seeds extract (BSE) showed very high antioxidant activity with free radical inhibition capacity of 14% and 12.60%, respectively. The obtained extracts were analyzed by gas chromatography and high-performance liquid chromatography, both combined with mass spectrometry detection (GC-MS, HPLC-MS). GC-MS analysis of the SPME extraction showed the presence of 29 compounds with isopentyl alcohol in major concentration (18.19%) in the alcoholic beer; on the other hand, the HPLC-DAD-ESI/MS analysis of the ethyl acetate extract showed the presence of 13 phenolic compounds. Interestingly, the degradation of 3-Hydroxyphloretin 2'-O-glucoside in the final products of the non-alcoholic beers was found. Finally, the FTIR analysis was also employed in order to detect the type of efficient groups present in the extracts.

Abstract Simple Summary Gametes are particularly susceptible to oxidative stress that impairs the reproductive function. This study was conducted to study the effect of a mitochondria-targeted dietary antioxidant (AntiOxBEN2) on bovine sperm function. Different doses of this antioxidant were tested during spermatozoa capacitation and/or fertilization processes. Spermatozoa mitochondrial function was improved when AntiOxBEN2 was supplemented to the capacitation medium. Supplementation of both capacitation and fertilization media with AntiOxBEN2 (lowest dose) improved the fertilization process and embryo production. Our results showed that AntiOxBEN2 can be used for the prevention of oxidative stress in bovine spermatozoa and may constitute a putative novel therapeutic strategy to improve the outcomes of assisted reproductive techniques. Sperm cells are particularly vulnerable to reactive oxygen species (ROS), impairing their fertilizing ability. Our objective was to study the effect of a novel mitochondrial-directed antioxidant, AntiOxBEN2, on bovine sperm function. This antioxidant was added to the semen capacitation medium (CAP), during the swim-up process, and to the fertilization medium (FERT) during the co-incubation of matured oocytes and capacitated spermatozoa, in concentrations of 0 (control), 1, and 10 mu M. After the swim-up, sperm motility (CASA and visual analysis), vitality (eosin-nigrosin), mitochondrial membrane potential (JC1), intracellular ROS, adenosine triphosphate (ATP) levels, and basal metabolism (Seahorse Xfe96) were evaluated. Embryo development and quality were also assessed. Higher cleavage rates were obtained when 1 mu M AntiOxBEN2 were added to CAP and FERT media (compared to control, p < 0.04). A positive effect of AntiOxBEN2 on intracellular ROS reduction (p = 0.01), on the increment of mitochondrial membrane potential (p <= 0.003) and, consequently, on the sperm quality was identified. However, the highest dose impaired progressive motility, ATP production, and the number of produced embryos. The results demonstrate a beneficial effect of AntiOxBEN2 (1 mu M) on sperm capacitation and fertilization processes, thus improving embryonic development. This may constitute a putative novel therapeutic strategy to improve the outcomes of assisted reproductive techniques (ART).

Abstract Thymus capitatus is a Mediterranean endemic plant commonly known as Zaitra in northern Morocco. As T. capitatus is widely used in traditional medicine and food, this present work aims to investigate the chemical compositions and biological activities of the T. capitatus leaves essential oil (TcLEO), acetonic (TcLAE), and methanolic extract (TcLME). The spectrophotometric determination demonstrated that T. capitatus is a natural source rich in phenolic contents (TPC) and flavonoid contents (TFC) and that TcLME revealed the highest TPC and TFC than TcLAE and TcLEO. The LC-MS analysis of phenolic compounds showed that paraben acid was predominant in both TcLME and TcLAE, followed by cinnamic acid and p-hydroxybenzoic acid. GC-MS analysis of the TcLEO revealed the presence of a total of 10 compounds, which were predominated by carvacrol. The antioxidant activity by ORAC was observed to be significantly higher in TcLEO and TcLAE than in TcLME. All samples used to assess DNA degradation effectively prevented DNA oxidation and, at the same time, had a prooxidant effect. The genotoxicity test showed that the T. capitatus were devoid of any mutagenic activity. Concerning antifungal activity, all samples were able to inhibit the growth of all microorganisms tested at low concentrations. TcLAE showed higher activity than TcLME, and in general, dermatophytes were more susceptible, being Microsporum canis the most sensitive one. Overall, the results obtained from this study confirm the wide uses of T. capitatus. Furthermore, the finding results suggest that the T. capitatus essential oil and extracts can be highly useful for pharmaceutical industries.

Abstract Parkinson's disease (PD) is an incurable neurodegenerative movement disorder. PD affects 2% of the population above 65 years old; however, with the growing number of senior citizens, PD prevalence is predicted to increase in the following years. Pathologically, PD is characterized by dopaminergic cell neurodegeneration in the substantia nigra, resulting in decreased dopamine levels in the nigrostriatal pathway, triggering motor symptoms. Although the pathological mechanisms leading to PD are still unclear, large evidence indicates that oxidative stress plays an important role, not only because it increases with age which is the most significant risk factor for PD development, but also as a result of alterations in several processes, particularly mitochondria dysfunction. The modulation of oxidative stress, especially using dietary mitochondriotropic antioxidants, represents a promising approach to prevent or treat PD. Although most mitochondria-targeted antioxidants with beneficial effects in PD-associated models have failed to show any therapeutic benefit in clinical trials, several questions remain to be clarified. Hereby, we review the role played by oxidative stress in PD pathogenesis, emphasizing mitochondria as reactive oxygen species (ROS) producers and as targets for oxidative stress-related dysfunctional mechanisms. In addition, we also describe the importance of using dietary-based mitochondria-targeted antioxidants as a valuable strategy to counteract the deleterious effects of ROS in pre-clinical and/or clinical trials of PD, pointing out their significance to slow, and possibly halt, the progression of PD.

Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal and rapidly progressing neurodegenerative disease that affects motor neurons. This disease is associated with oxidative stress especially in mutant superoxide dismutase 1 (mutSOD1) patients. However, less is known for the most prevalent sporadic ALS form, due to a lack of disease models. Here, we studied oxidative stress profiles in lymphoblasts from ALS patients with mutSOD1 or unknown (undSOD1) mutations. Methods mutSOD1 and undSOD1 lymphoblasts, as well as sex/age-matched controls (3/group) were obtained from Coriell and divided into 46 years-old-men (C1), 46 years-old-women (C2) or 26/27 years-old-men (C3) cohorts. Growth curves were performed, and several parameters associated with redox homeostasis were evaluated, including SOD activity and expression, general oxidative stress levels, lipid peroxidation, response to oxidative stimulus, glutathione redox cycle, catalase expression, and activity, and Nrf2 transcripts. Pooled (all cohorts) and paired (intra-cohort) statistical analyses were performed, followed by clustering and principal component analyses (PCA). Results Although a high heterogeneity among lymphoblast redox profiles was found between cohorts, clustering analysis based on 7 parameters with high chi-square ranking (total SOD activity, oxidative stress levels, catalase transcripts, SOD1 protein levels, metabolic response to mM concentrations of tert-butyl hydroperoxide, glutathione reductase activity, and Nrf2 transcript levels) provided a perfect cluster segregation between samples from healthy controls and ALS (undSOD1 and mutSOD1), also visualized in the PCA. Conclusions Our results show distinct redox signatures in lymphoblasts from mutSOD1, undSOD1 and healthy controls that can be used as therapeutic targets for ALS drug development.

Abstract Over the years, literature reported inumerous applications of electrochemical and surface plasmon resonance (SPR) immunoassays for biosensing but, so far, the combination of the two methods in the same sensing spot for analytical purposes is much less explored and discussed. The aim of this Review is to highlight the great potential of electrochemistry combined-SPR (eSPR) as analytical tool for screening chemically and biologically relevant (bio)molecules by combining the unique features of SPR integrated with electrochemical readout.In the first part of the Review, we describe the urgent need of innovative methods for screening clinical biological markers (General Introduction), briefly discuss general concepts of SPR and electrochemical sensing (Concepts behind eSPR biosensors) and highlight the hyphenation of two methods to developed combined biosensing systems (Set-up configuration and eSPR principles). Firstly, we briefly give an overview of the setup for implementation of eSPR technique and discuss some relevant experimental conditions to perform the combined optical and electrochemical measurements. Then, the principles and fundamentals of eSPR biosensors are presented and described. We also present representative examples of eSPR biosensors in the literature (Applications of eSPR biosensors).In the second part, we review studies on how combined electrical and plasmonic detection contributed to the biosensing field, in particular, for the successful screening of clinically relevant biomolecules, namely proteins (Detection of proteins), nucleic acids (Detection of nucleic acids), small size chemical species (Detection of small molecules) and cells (Living-cell Analysis).Finally, we discuss the current limitations of eSPR biosensors performance and suggest possible ways to overcome these limitations (Limitations and optimization) and then we explore aspects about the development of the method and its applications and discuss areas of likely future growth (Conclusions and perspectives). (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract UV-based advanced oxidation processes (AOPs) (UV/H2O2 and UV/S2O82-) with a titanium(IV)-doped carbon dot, TiP-CD, as a catalyst were developed for the decomposition of Remazol Brilliant Blue R (Reactive Blue 19), an anthraquinone textile dye (at T = 25 degrees C and pH = 7). The Ti-CD, with marked catalytic UV properties, was successfully synthesized by the one-pot hydrothermal procedure, using L-cysteine as carbon precursor, ethylenediamine as nitrogen source, PEG (polyethylene glycol) as a capping agent, and titanium(IV) isopropoxide (precursor of TiO2 doping). Contrary to azo dyes (methyl orange, orange II sodium salt, and reactive black 5), which achieved complete degradation in a time interval less than 30 min in the developed AOP systems (UV/H2O2, UV/S2O82-, and UV/TiO2), the RBB-R showed relatively low degradation rates and low discoloration rate constants. In the presence of the catalyzer, the reaction rate significantly increased, and the pseudo-first-order rate constants for the RBB-R discoloration were UV/3.0 mM H2O2/TIP-CD-0.0330 min(-1) and UV/1.02 mM S2O82-/TIP-CD-0.0345 min(-1).

Abstract The absence of disease modifying drugs in Parkinson's disease therapy urges for new chemical entities acting on relevant PD-associated biological targets. As a result, developing selective and reversible inhibitors targeting MAO-B is still a desirable line of therapeutic research. Within this framework, a small library of chromone derivatives was synthesized and screened towards human monoamine oxidases. Structural modifications on the chromone 3-phenylcarboxamide resulted in potent MAO-B inhibitors with an improved drug-like profile, and for the first time we obtained potent and selective chromone 2-phenylcarboxamides acting in the low nanomolar range. Compounds 5-hydroxy-4-oxo-N-phenyl-4H-chromene-3-carboxamide (38) (IC50 = 13.0 nM) and N-(4-chlorophenyl)-5-hydroxy-4-oxo-4H-chromene-3-carboxamide (41) (IC50 = 8.3 nM) stood out as reversible, potent, selective and non-cytotoxic MAO-B inhibitors bearing a favourable drug-like profile. Both compounds displayed cytoprotective effects towards iron(III) oxidative stressor.