Browsing by Author "Garrido, Jorge"
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- An Electrochemical Outlook on Tamoxifen Biotransformation: Current and Future ProspectsPublication . Garrido, Jorge; Garrido, E. Manuela; Oliveira-Brett, Ana Maria; Borges, FernandaTamoxifen is a nonsteroidal antiestrogen that is currently and widely used in the treatment of breast cancer in all of its stages, in adjuvant therapy as a long-term suppressant of tumor recurrence and also as a chemopreventive agent in women that are in high risk of developing this type of estrogen-dependent cancer. From a toxicological and (bio)analytical point of view the knowledge of the metabolic pathways of a drug is found to be extremely important. So, in the present work the most important tamoxifen biotransformation steps were reviewed in the light of recent pharmacological data. This overview also includes the current controversy concerning tamoxifen DNA-damaging (genotoxic) versus non-genotoxic mechanisms. A special focus will be given to the putative application of electrochemical methods as a modern and reliable analytical tool for determination of tamoxifen and its metabolites. Moreover, the potential of DNA electrochemical sensors for detection of structural damage to DNA as a basis for toxicity screening is highlighted. Future prospects looking for the importance of developing new analytical methodologies are also discussed.
- Antioxidant properties of hydroxycinnamic acids: a review of structure- activity relationshipsPublication . Razzaghi-Asl, N.; Garrido, Jorge; Khazraei, H.; Borges, Fernanda; Firuzi, O.Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful for management of oxidative stress-related diseases.
- Bonding to Psychedelics: Synthesis of Molecularly Imprinted Polymers Targeting 4-Bromo-2,5-dimethoxyphenethylamine (2C-B)Publication . Martins, Daniel; Fernandes, Carlos; Mendes, Ricardo F.; Cagide, Fernando; Silva, António Fernando; Borges, Fernanda; Garrido, Jorge; Garrido, JorgeThe increasing interest in utilizing psychedelics for therapeutic purposes demands the development of tools capable of efficiently monitoring and accurately identifying these substances, thereby supporting medical interventions. 4-Bromo-2,5-dimethoxyphenethylamine (2C-B) has gained significant popularity as one of the most widely used psychedelic compounds in non-medical settings. In this study, we aimed to create a material with selective recognition of 2C-B by synthesizing a series of molecularly imprinted polymers (MIP) using 2C-B as the template and varying ratios of methacrylic acid (MAA) as the functional monomer (1:2, 1:3, and 1:4). Both thermal and microwave-assisted polymerization processes were employed. The molar ratio between the template molecule (2C-B) and functional monomer (MAA) was 1:4, utilizing a microwave-assisted polymerization process. Isotherm studies revealed a Langmuir’s maximum absorption capacity (Bmax) value of 115.6 μmol·mg−1 and Kd values of 26.7 μM for this material. An imprint factor of 4.2 was determined for this material, against the corresponding non-imprinted polymer. The good selectivity against 14 other new psychoactive substances highlighted the material’s potential for applications requiring selective recognition. These findings can contribute to the development of tailored materials for the detection and analysis of 2C-B, supporting advancements in non-medical use monitoring and potential therapeutic models involving psychedelics.
- Boosting caffeic acid performance as antioxidant and monoamine oxidase B/catechol-O-methyltransferase inhibitorPublication . Chavarria, Daniel; Benfeito, Sofia; Soares, Pedro; Lima, Carla; Garrido, Jorge; Serrão, Paula; Soares-da-Silva, Patrício; Remião, Fernando; Oliveira, Paulo J.; Borges, FernandaIncreased oxidative stress (OS) and depletion of nigrostriatal dopamine (DA) are closely linked to the neurodegeneration observed in Parkinson’s Disease (PD). Caffeic acid (CA)-based antioxidants were developed, and their inhibitory activities towards monoamine oxidases (MAOs) and catechol O-methyltransferases (COMT) were screened. The results showed that the incorporation of an extra double bond maintained or even boosted the antioxidant properties of CA. α-CN derivatives displayed redox potentials (Ep) similar to CA (1) and inhibited hMAO-B with low μM IC50 values. Moreover, catechol amides acted as MB-COMT inhibitors, showing IC50 values within the low μM range. In general, CA derivatives presented safe cytotoxicity profiles at concentrations up to 10 μM. The formation of reactive oxygen species (ROS) induced by CA derivatives may be underlying the cytotoxic effects observed at higher concentrations. Catechol amides 3–6, 8–11 at 10 μM protected cells against oxidative damage. Compounds 3 and 8 were predicted to cross the blood-brain barrier (BBB) by passive diffusion. In summary, we report for the first time BBB-permeant CA-based multitarget lead compounds that may restore DAergic neurotransmission (dual hMAO-B/MB-COMT inhibition) and prevent oxidative damage. The data represents a groundbreaking advancement towards the discovery of the next generation of new drugs for PD.
- Carbon nanotube β-cyclodextrin-modified electrode for quantification of cocaine in seized street samplesPublication . Garrido, Jorge; Borges, F.; Brett, C. M. A.; Garrido, E. ManuelaDetection and quantification of cocaine is a key tool in fields such as police apprehensions and the fight against drug trafficking. Thus, a simple, fast and inexpensive electroanalytical methodology for the determination of cocaine in seized street samples has been developed, employing linear sweep voltammetry. The method is based on the use of a glassy carbon (GC) electrode modified by a combination of multi-walled carbon nanotubes (MWCNT) with β- cyclodextrin (β-CD) incorporated in a polyaniline film. The proposed method shows high reproducibility, repeatability and specificity. Under optimal conditions, the β-CD/ MWCNT-modified GC electrode gives a detection limit of 1.02 μM cocaine. The results obtained are in good agreement with those obtained by the high-performance liquid chromatography reference method. The new methodology proposed has excellent potential as the basis of a portable analytical sensor for on-site screening of cocaine in seized street samples.
- Characterization of an antioxidant surfactant-free topical formulation containing Castanea sativa leaf extractPublication . Almeida, Isabel F.; Maleckova, Jitka; Saffi, Raquel; Monteiro, Helena; Góios, Filipa; Amaral, Maria Helena; Costa, Paulo Cardoso; Garrido, Jorge; Silva, Paulo; Pestana, Nazaré; Bahia, Maria FernandaContext: Inclusion of antioxidants in topical formulations can contribute to minimize oxidative stress in the skin, which has been associated with photoaging, several dermatosis and cancer. Objective: A Castanea sativa leaf extract with established antioxidant activity was incorporated into a semisolid surfactant-free formulation. The objective of this study was to perform a comprehensive characterization of this formulation. Materials and methods: Physical, microbiological and functional stability were evaluated during 6 months storage at 20 °C and 40 °C. Microstructure elucidation (cryo-SEM), in vitro release and in vivo moisturizing effect (Corneometer® CM 825) were also assessed. Results and discussion: Minor changes were observed in the textural and rheological properties of the formulation when stored at 20 °C for 6 months and the antioxidant activity of the plant extract remained constant throughout the storage period. Microbiological quality was confirmed at the end of the study. Under accelerated conditions, higher modifications of the evaluated parameters were observed. Cryo-SEM analysis revealed the presence of oil droplets dispersed into a gelified external phase. The release rate of the antioxidant compounds (610 ± 70 µgh−0.5) followed Higuchi model. A significant in vivo moisturizing effect was demonstrated, that lasted at least 4 h after product’s application. Conclusion: The physical, functional and microbiological stability of the antioxidant formulation was established. Specific storage conditions should be recommended considering the influence of temperature on the stability. A skin hydration effect and good skin tolerance were also found which suggests that this preparation can be useful in the prevention or treatment of oxidative stress-mediated dysfunctions.
- Chromone: A valid scaffold in medicinal chemistryPublication . Gaspar, Alexandra; Matos, Maria João; Garrido, Jorge; Uriarte, Eugénio; Borges, FernandaChromones are a group of naturally occurring compounds that are ubiquitous in nature, especially in plants. The word chromone is derived from the Greek word chroma, meaning “color”, which point out that many chromone derivatives can exhibit a diversity of colors.
- Comparative Studies on the Photoreactivity, Efficacy, and Safety of Depigmenting AgentsPublication . Mota, Sandra; Rosa, Gonçalo P.; Barreto, Maria Carmo; Garrido, Jorge; Sousa, Emília; Cruz, Maria T.; Almeida, Isabel F.; Quintas, Clara; Garrido, Jorge; Mordon, SergeDepigmenting products are increasingly used to counteract skin hyperpigmentation and related psychosocial issues. This study aimed to compare different depigmenting agents—4-butylresorcinol; bakuchiol; tranexamic acid; ascorbyl glucoside; α-arbutin; and ascorbic acid—for photoreactivity; tyrosinase inhibition; and safety. Photoreactivity was assessed using the Reactive Oxygen Species assay. In vitro tyrosinase inhibition was compared, and cell viability was assessed in B-16V melanocytes to evaluate safety. Results showed 4-butylresorcinol, ascorbyl glucoside, and α-arbutin are non-photoreactive, while for ascorbic acid and bakuchiol it was not possible to reach conclusive results due to the lack of specificity of the ROS assay. 4-Butylresorcinol, acting as a competitive inhibitor, displayed potent tyrosinase inhibition, followed by ascorbic acid and bakuchiol. Both 4-butylresorcinol and bakuchiol reduced cell viability in a concentration-dependent manner. The insights obtained in this work support the development of depigmenting products by providing useful scientific guidance on the photostability, tyrosinase inhibitory efficacy, and skin safety of depigmenting agents.
- Comparative studies on the photoreactivity, efficacy, and safety of depigmenting agentsPublication . Mota, Sandra; Rosa, Gonçalo P.; Barreto, Maria Carmo; Garrido, Jorge; Sousa, Emília; Cruz, Maria T.; Almeida, Isabel F.; Quintas, ClaraDepigmenting products are increasingly used to counteract skin hyperpigmentation and related psychosocial issues. This study aimed to compare different depigmenting agents—4-butylresorcinol; bakuchiol; tranexamic acid; ascorbyl glucoside; α-arbutin; and ascorbic acid—for photoreactivity; tyrosinase inhibition; and safety. Photoreactivity was assessed using the Reactive Oxygen Species assay. In vitro tyrosinase inhibition was compared, and cell viability was assessed in B-16V melanocytes to evaluate safety. Results showed 4-butylresorcinol, ascorbyl glucoside, and α-arbutin are non-photoreactive, while for ascorbic acid and bakuchiol it was not possible to reach conclusive results due to the lack of specificity of the ROS assay. 4-Butylresorcinol, acting as a competitive inhibitor, displayed potent tyrosinase inhibition, followed by ascorbic acid and bakuchiol. Both 4-butylresorcinol and bakuchiol reduced cell viability in a concentration-dependent manner. The insights obtained in this work support the development of depigmenting products by providing useful scientific guidance on the photostability, tyrosinase inhibitory efficacy, and skin safety of depigmenting agents.
- Design of an Emulgel for Psoriasis Focused on Patient PreferencesPublication . Oliveira, Rita Sanches; da Silva, Diva Ferraz; Mota, Sandra; Garrido, Jorge; Garrido, E. Manuela; Lobo, José Manuel Sousa; Almeida, Isabel FilipaAdherence to topical treatments is low and is known to be influenced by the vehicle properties. Betamethasone dipropionate (BD) is an anti-inflammatory steroid, used in psoriasis treatment in the form of an ointment, cream, or solution. The aim of this work was to develop a new vehicle for BD, focusing on the preferences of patients with psoriasis as a strategy to improve treatment adherence. Two vehicles with an aqueous external phase were explored: an emulgel and a hydrogel based on a cyclodextrin inclusion complex used to improve the aqueous solubility of BD. Since BD solubilization was not fully achieved in the hydrogel, only the emulgel was selected for further characterization. This new vehicle (emulgel) is characterized by its white, shiny appearance and good spreading properties. In comparison with petrolatum, a lower residue, higher evaporation rate, lower stickiness, and reduced ability to stain polyester fabric were observed. This vehicle also showed shear thinning behavior. The impact of this new vehicle on adherence to topical treatments should be further confirmed in clinical settings.