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    Bioactivación del quimioterapéutico ciclofosfamida mediada por citocromos P450 con fines de uso en terapia génica de cáncer
    (Universidad Tecnica del Norte, 2025-01-31)
    Saskya Carrera-Pacheco
    ;
    Esta revisión examina el papel de las enzimas del citocromo P450 en la bioactivación del agente quimioterapéutico ciclofosfamida (CPA) para uso en la terapia génica del cáncer. El estudio explora enzimas específicas del citocromo P450, como CYP2B6, CYP2C9 y CYP3A4, encargadas de metabolizar la CPA en su forma activa, destacando su potencial en la terapia del gen suicida o GDEPT. La revisión también analiza las modificaciones genéticas realizadas para mejorar la eficiencia catalítica de estas enzimas y aborda los desafíos y las direcciones futuras de la integración de GDEPT con otras terapias contra el cáncer para mejorar la especificidad y eficacia del tratamiento.
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    Designing cytochrome P450 enzymes for use in cancer gene therapy
    (Frontiers Media SA, 2024-05-24)
    Saskya E. Carrera-Pacheco
    ;
    Alexander Mueller
    ;
    Juan A. Puente-Pineda
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    ;
    Cancer is a significant global socioeconomic burden, as millions of new cases and deaths occur annually. In 2020, almost 10 million cancer deaths were recorded worldwide. Advancements in cancer gene therapy have revolutionized the landscape of cancer treatment. An approach with promising potential for cancer gene therapy is introducing genes to cancer cells that encode for chemotherapy prodrug metabolizing enzymes, such as Cytochrome P450 (CYP) enzymes, which can contribute to the effective elimination of cancer cells. This can be achieved through gene-directed enzyme prodrug therapy (GDEPT). CYP enzymes can be genetically engineered to improve anticancer prodrug conversion to its active metabolites and to minimize chemotherapy side effects by reducing the prodrug dosage. Rational design, directed evolution, and phylogenetic methods are some approaches to developing tailored CYP enzymes for cancer therapy. Here, we provide a compilation of genetic modifications performed on CYP enzymes aiming to build highly efficient therapeutic genes capable of bio-activating different chemotherapeutic prodrugs. Additionally, this review summarizes promising preclinical and clinical trials highlighting engineered CYP enzymes’ potential in GDEPT. Finally, the challenges, limitations, and future directions of using CYP enzymes for GDEPT in cancer gene therapy are discussed.
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    Relationship Between Bioactive Compounds and Biological Activities (Antioxidant, Antimicrobial, Antihaemolytic) of ‘Colcas’ Fruits at Different Stages of Maturity
    (MDPI AG, 2025-09-10)
    Elena Coyago-Cruz
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    ;
    Gabriela Méndez
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    Aida Guachamin
    ;
    Ruth Escobar-Quiñonez
    The genus Miconia is used in traditional medicine, but there are few studies supporting the bioactive potential of Miconia crocea. This study aimed to evaluate the physicochemical properties, bioactive compound content, and antioxidant, antimicrobial and antihaemolytic activities at four different phenological stages of M. crocea. The pH, soluble solids, titratable acidity, moisture and ash content were determined. Mineral contents were determined by atomic absorption. Vitamin C, organic acids, carotenoids, chlorophylls and derivatives and phenols were determined by chromatography. Total anthocyanins were determined by spectrophotometry. The antioxidant capacity was evaluated using ABTS and DPPH assays, and the antimicrobial activity was tested against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus mutans, Candida albicans and Candida tropicalis. Potassium was the predominant mineral (>1000 mg/100 g DW), while malic acid was the predominant organic acid. Lutein was the most abundant carotenoid, as among the phenolic compounds, m-coumaric acid and chlorogenic acid were most abundant (>1000 mg/100 g DW). The optimal method for preparing the extract for antimicrobial and haemolytic activity, with a focus on phenols, involved using 50% ethanol, applying ultrasound for six minutes, and carrying out three extractions. The M0% extract exhibited the most potent antimicrobial activity against S. mutans (MIC: 7.8 mg/mL). Anti-haemolytic activity indicates biocompatibility. The results emphasise the bioactive and antimicrobial potential of M. crocea, suggesting its possible application in various industries. However, further research is needed in the form of in vivo studies.
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    Phytochemical Composition and Biological Properties of Macleania rupestris Fruit Extract: Insights into Its Antimicrobial and Antioxidant Activity
    (MDPI AG, 2025-03-27) ; ;
    Elena Coyago-Cruz
    ;
    ;
    Jéssica Guamán-Bautista
    Macleania rupestris, a fruit-bearing species of the Ericaceae family, has traditionally been used for its potential medicinal properties. Background/Objectives: This study investigates the phytochemical composition and antimicrobial activity of M. rupestris fruit extract, focusing on its antibacterial, antibiofilm, and antifungal effects. Methods: M. rupestris (Kunth) A.C.Sm. berries (code: 4456, Herbario QUPS-Ecuador) were collected from the cloud forest Montano Alto, Cuenca-Ecuador, and the extract was obtained using an ethanolic-based extraction and chemically characterized. The antibacterial and antifungal activity of the fruit extract was assessed against seven multidrug-resistant bacteria strains and four fungal strains using the microdilution method. The biofilm inhibition potential was evaluated using a microplate assay with the crystal violet staining method. The antioxidant activity was evaluated using DPPH and ABTS assays. Results: The bioactive compounds showed 853.9 mg phenols/100 g DW, 573.2 mg organic acid/100 g DW, and 21.5 mg C-3-gl/100 g DW of anthocyanins. The antibacterial assays demonstrated significant inhibitory activity against Enterococcus faecalis, Enterococcus faecium, Escherichia coli, and Staphylococcus epidermidis, with MIC values ranging from 1.25 to 5 mg/mL. Additionally, the biofilm inhibition assays confirmed the potential of M. rupestris extract to disrupt bacterial biofilms, particularly in S. aureus and L. monocytogenes. Nevertheless, no significant antifungal activity was observed against Candida spp., suggesting selective antimicrobial properties. Finally, the antioxidant activity was strong (1.62 mmol TE/100 g DW by DPPH and 3.28 mmol TE/100 g DW by ABTS). Conclusions: These findings indicate that M. rupestris possesses promising antibacterial, antibiofilm, and antioxidant properties, which may be attributed to its phenolic and organic acid composition. Further fractionation and targeted bioassays are required to elucidate the specific bioactive compounds responsible for these effects and explore their potential applications in antimicrobial formulations.
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    Phytosynthesis of Silver Nanoparticles Using Mansoa alliacea (Lam.) A.H. Gentry (Bignoniaceae) Leaf Extract: Characterization and Their Biological Activities
    (MDPI AG, 2024-09-25) ;
    Saskya E. Carrera-Pacheco
    ;
    ; ;
    Cristina Rodríguez-Pólit
    Background. Mansoa alliacea is a native plant renowned for its medicinal properties in traditional healing in the Amazon Region. This plant is rich in polyphenols, flavonoids, anthocyanins, phenolic acids, tannins, ketones, triterpenes, as well as other bioactive compounds. Objectives. This study aims to develop an innovative, eco-friendly method for synthesizing silver nanoparticles using an aqueous extract of M. alliacea (Ma-AgNPs), enhancing the biological activities of AgNPs by leveraging the therapeutic potential of the plant’s bioactive compounds. Methods. Silver nanoparticles were synthesized using the aqueous extract of M. alliacea. The biological activities of Ma-AgNPs were assessed, including antibacterial, anti-inflammatory, antioxidant, antitumor, and anti-biofilm effects, along with evaluating their hemolytic activity. Results. Quantitative analysis revealed that Ma-AgNPs exhibit potent antibacterial activity against multidrug and non-multidrug-resistant bacteria, with MIC values ranging from 1.3 to 10.0 µg/mL. The Ma-AgNPs significantly reduced NO production by 86.9% at 4 µg/mL, indicating strong anti-inflammatory effects. They demonstrated robust antioxidant activity with an IC50 of 5.54 ± 1.48 µg/mL and minimal hemolytic activity, with no hemolysis observed up to 20 µg/mL and only 4.5% at 40 µg/mL. Their antitumor properties were notable, with IC50 values between 2.9 and 5.4 µg/mL across various cell lines, and they achieved over 50% biofilm inhibition at concentrations of 30–40 µg/mL. Conclusions. These findings underscore the potential of Ma-AgNPs for biomedical applications, particularly in developing new antimicrobial agents and bioactive coatings with reduced toxicity. This research highlights a sustainable approach that not only preserves but also amplifies the inherent biological activities of plant extracts, paving the way for innovative therapeutic solutions.
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    Bioactive Phenolic Compounds from Rambutan - Nephelium lappaceum L. - Shell: Encapsulation, Structural Stability, and Multifunctional Activities
    (MDPI AG, 2025-11-09)
    Carlos Barba Ostria
    ;
    Orestes López
    ;
    Alexis Debut
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    ;
    Rambutan (Nephelium lappaceum) shell, an agro-industrial by-product, is a rich source of phenolic acids and minor anthocyanins, but its direct use is limited by instability and low bioavailability. We extracted phenolic-rich fractions and produced maltodextrin microcapsules by spray drying, then confirmed chemical entrapment and amorphization by FTIR, SEM, and XRD. The formulation showed high encapsulation efficiency and high antioxidant capacity (DPPH), selective bactericidal activity against Pseudomonas aeruginosa and Burkholderia cepacia, and strong inhibition of Staphylococcus aureus and Listeria monocytogenes biofilms, while exhibiting negligible hemolysis (&lt;2%) across tested concentrations. Antitumor effects were moderate with low selectivity in vitro, indicating that phenolic-acid-driven redox modulation may require fractionation or delivery optimization for oncology applications. Overall, spray-dried microcapsules provided structural stability and safety while concentrating multifunctional activities relevant to food and biomedical uses. By valorizing a tropical waste stream into a bioactive, hemocompatible ingredient, this work aligns with societal goals on health and sustainable production (SDG 3 and SDG 12) and offers a scalable route to deploy underutilized phenolic resources.</jats:p>
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    Current Landscape of Methods to Evaluate Antimicrobial Activity of Natural Extracts
    (MDPI AG, 2023-01-20) ;
    Saskya E. Carrera-Pacheco
    ;
    ;
    Cristina Rodríguez-Pólit
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    <jats:p>Natural extracts have been and continue to be used to treat a wide range of medical conditions, from infectious diseases to cancer, based on their convenience and therapeutic potential. Natural products derived from microbes, plants, and animals offer a broad variety of molecules and chemical compounds. Natural products are not only one of the most important sources for innovative drug development for animal and human health, but they are also an inspiration for synthetic biology and chemistry scientists towards the discovery of new bioactive compounds and pharmaceuticals. This is particularly relevant in the current context, where antimicrobial resistance has risen as a global health problem. Thus, efforts are being directed toward studying natural compounds’ chemical composition and bioactive potential to generate drugs with better efficacy and lower toxicity than existing molecules. Currently, a wide range of methodologies are used to analyze the in vitro activity of natural extracts to determine their suitability as antimicrobial agents. Despite traditional technologies being the most employed, technological advances have contributed to the implementation of methods able to circumvent issues related to analysis capacity, time, sensitivity, and reproducibility. This review produces an updated analysis of the conventional and current methods to evaluate the antimicrobial activity of natural compounds.</jats:p>
    Scopus© Citations 82
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    Bioactive Properties of Microencapsulated Anthocyanins from Vaccinium floribundum and Rubus glaucus
    (MDPI AG, 2024-11-21)
    Carlos Barba-Ostria
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    ;
    Castillo-solís Fabián
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    Saskya E. Carrera-Pacheco
    ;
    Orestes Lopez
    Anthocyanins, widely recognized for their antioxidant properties and potential health benefits, are highly susceptible to degradation due to environmental factors such as light, temperature, and pH leading to reduced bioavailability and efficacy. Microencapsulation, which involves entrapment in a matrix to enhance stability and bioavailability. This study aims to investigate the bioactive properties of microencapsulated anthocyanins derived from Vaccinium floribundum (Andean blueberry) and Rubus glaucus (Andean blackberry). The extracts from V. floribundum and R. glaucus were microencapsulated using maltodextrin as the carrier agent due to its film-forming properties and effectiveness in stabilizing sensitive compounds through a spray-drying process. The microcapsules were characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) to assess their chemical and morphological properties. The biological activities of these microencapsulated anthocyanins were evaluated using in vitro assays for their antibacterial, antioxidant, and anti-inflammatory effects. The results indicated enhanced bioactivity of the microencapsulated anthocyanins, suggesting their potential use in developing functional foods and pharmaceuticals. This study provides valuable insights into the effectiveness of microencapsulation in preserving anthocyanins’ functional properties and enhancing their health-promoting effects, highlighting the potential for application in the food and pharmaceutical industries.
    Scopus© Citations 9
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    Experimental and computational studies of Schiff bases derived from 4-aminoantipyrine as potential antibacterial and anticancer agents
    (Springer Science and Business Media LLC, 2025-01-31) ; ;
    Saskya E. Carrera Pacheco
    ;
    Cristina Rodríguez-Pólit
    ;
    Carlos Barba-Ostria
    Schiff bases are organic compounds recognized for their biological activities, including antiviral, antibacterial, antifungal, and anticancer properties, making them promising candidates in medicinal chemistry. In this studio, a series of Schiff bases derived from 4-aminoantipyrine and substituted cinnamaldehydes were evaluated in vitro against liver (HepG2) and thyroid (THJ29T) cancer cells, Gram-positive and Gram-negative multidrug-resistant bacteria, and biofilm-forming pathogens. Six compounds demonstrated anticancer activity, though some exhibited toxicity to non-tumor cells. Compounds showed notable anticancer potential, while also exhibited strong antibacterial effects, with being the most effective against multidrug-resistant bacteria strains. These Schiff bases also inhibit biofilm formation, suggesting their potential for treating biofilm-related infections. analyses of their ADME properties, global reactivity descriptors, and binding affinities corroborated these findings. The Schiff base has a strong binding affinity for DNA gyrase and vitamin D receptor, suggesting potential mechanisms for its antibacterial and anticancer activities.