Mónica Ávila Murillo

An eco-friendly method for the synthesis of oxa-bridged-1-benzazepines employing Piper auritum essential oil as a renewable starting material is described.

Deep eutectic solvents (DESs) have emerged as sustainable alternatives to conventional or-ganic solvents for the extraction of bioactive natural products. This study developed a green extraction strategy for recovering neuroactive alkaloids from Bocconia frutescens roots using DES-based systems. Thirteen DES formulations were evaluated and compared with conven-tional aqueous and ethanolic extraction. UHPLC-DAD and UHPLC-ESI-HRMS analyses iden-tified sanguinarine and chelerythrine as the major benzophenanthridine alkaloids present in the extracts. Among the solvents tested, a citric acid–glucose (1:1) DES exhibited the highest extraction efficiency. Extraction parameters were optimized using a Box–Behnken response surface design, evaluating the effects of plant material-to-solvent ratio, temperature, and effect of water addition. Under optimized conditions, alkaloid recovery increased four-fold com-pared with the central experimental point, reaching a maximum alkaloids concentration of 400.1 ppm. The optimized alkaloid-rich extract displayed potent neuroprotective activity, in-hibiting acetylcholinesterase and butyrylcholinesterase with IC₅₀ values of 2.96 and 46.79 μg/mL, respectively. Additionally, the extract strongly inhibited Aβ₁₋₄₂ aggregation, exhibiting an IC₅₀ value of 0.70 μg/mL. These results demonstrate that DES-assisted extraction is an effi-cient and environmentally sustainable approach for obtaining alkaloid-enriched extracts from B. frutescens and highlight their potential as multitarget neuroprotective agents for Alzheimer's disease management.

Agro-industrial byproducts from Colombian Passiflora species represent an underexplored source of chemically diverse metabolites with promising cosmetic and pharmaceutical potential. This study investigated the chemical profiles and photoprotective potential of polar extracts obtained from byproducts (leaves, pericarps, and seeds) of six commercially relevant Passiflora species cultivated in Colombia (P. ligularis, P. edulis var. edulis, P. edulis var. flavicarpa, P. maliformis, P. quadrangularis and P. tarminiana × P. tripartita). Butanolic fractions from leaves and pericarps and hydroethanolic seed extracts were analyzed using ¹H NMR, GC-FID, GC-MS and UHPLC-qTOF. NMR profiling revealed aromatic signals mainly associated with flavonoids and stilbenoids in leaves and pericarps, while seeds exhibited abundant fatty acids, particularly linoleic acid. Molecular networking enabled the visualization of chemical diversity and supported the identification of 74 metabolites, including flavonoids, saponins, and stilbenoids, using Global Natural Products Social Molecular Networking (GNPS), SIRIUS (Version 6.0.5) software, and comparison with the literature. In vitro spectrophotometric photoprotective evaluation using the Mansur equation at 200 ppm showed that leaf extracts exhibited the highest sun protection factor (SPF) values, followed by seeds and pericarps, consistent with their phenolic composition. All active extracts demonstrated broad-spectrum protection, with high UVA ratios and critical wavelength values. These findings highlight the potential of Passiflora byproducts as sustainable sources of natural photoprotective agents for cosmetic applications.

Fungal endophytes have emerged as a promising source of bioactive compounds with potent antifungal properties for plant disease management. This study aimed to isolate and characterize fungal endophytes from Antillean avocado (Persea americana var. americana) trees in the Colombian Caribbean, capable of producing bio-fungicide metabolites against Fusarium solani and Fusarium equiseti. For this, dual culture assays, liquid-state fermentation of endophytic isolates, and metabolite extractions were conducted. From 88 isolates recovered from leaves and roots, those classified within the Diaporthe genus exhibited the most significant antifungal activity. Some of their organic extracts displayed median inhibitory concentrations (IC₅₀) approaching 200 μg/mL. To investigate the mechanism of action, in silico studies targeting chitin synthase (CS) were performed, including homology models of the pathogens’ CS generated using Robetta, followed by molecular docking with Vina and interaction fingerprint similarity analysis of 15 antifungal metabolites produced by Diaporthe species using PROLIF. A consensus scoring strategy identified diaporxanthone A (12) and diaporxanthone B (13) as the most promising candidates, achieving scores up to 0.73 against F. equiseti, comparable to the control Nikkomycin Z (0.82). These results suggest that Antillean avocado endophytes produce bioactive metabolites that may inhibit fungal cell wall synthesis, offering a sustainable alternative for disease management.

Moniliophthora roreri is a major fungal pathogen that significantly reduces cacao yields in Colombia. Currently, farmers rely solely on fungicides for its control, and environmentally friendly alternatives remain limited. The objective of this study was to assess the antagonistic potential of yeasts isolated from diverse niches in Colombia against M. roreri as a first step toward developing sustainable biocontrol strategies. Initially, the pathogen was identified at the molecular level. Subsequently, seven yeast strains belonging to the genera Wickerhamomyces, Naganishia, Pichia, and Metschnikowia were assessed for antifungal activity against M. roreri, volatile organic compounds (VOCs) production, and enzymatic activities. Although none of the strains inhibited fungal growth through direct confrontation, VOC-mediated antagonism in dual-culture assays resulted in pathogen growth inhibition ranging from 38% to 98%. Glucanase, protease, and cellulase activities were detected to varying degrees among the isolates. Pichia kluyveri Lv125, which exhibited the strongest inhibitory effect, was selected for VOC characterization using gas chromatography-mass spectrometry (GC–MS). Antagonistic VOCs produced after 15 days of incubation included 1-butanol, 3-methylbutanoic acid, butanoic acid, 3-methyl-1-butanol, 3-methyl acetate, and phenylethyl alcohol. These findings highlight the potential of yeasts as biological control agents and support their use as an alternative management strategy against M. roreri in cacao plantations.

Fungal endophytes have emerged as a promising source of bioactive compounds with potent antifungal properties for plant disease management. This study aimed to isolate and characterize fungal endophytes from Antillean avocado (Persea americana var. americana) trees in the Colombian Caribbean, capable of producing bio-fungicide metabolites against Fusarium solani and Fusarium equiseti. For this, dual-culture assays, liquid-state fermentation of endophytic isolates, and metabolite extractions were conducted. From 88 isolates recovered from leaves and roots, those classified within the Diaporthe genus exhibited the most significant antifungal activity. Their organic extracts displayed median inhibitory concentrations (IC₅₀) approaching 200 μg/mL. To investigate the mechanism of action, in silico studies targeting Chitin Synthase (CS) were performed, including homology models of the pathogens' CS generated using Robetta, followed by molecular docking with Vina, and interaction fingerprint similarity analysis of 15 antifungal metabolites produced by Diaporthe species using PROLIF. A consensus scoring strategy identified diaporxanthone A (12) and diaporxanthone B (13) as the most promising candidates, achieving scores up to 0.73 against F. equiseti, comparable to the control Nikkomycin Z (0.82). These results suggest that Antillean avocado endophytes produce bioactive metabolites that may inhibit fungal cell wall synthesis, offering a sustainable alternative for disease management.

Lipid metabolism is a vital biological process essential for human health, encompassing key pathways necessary for the survival and homeostasis of all organisms. Liver X Receptors (LXRs) are extensively acknowledged as pivotal regulators of lipid homeostasis and inflammatory responses. Pharmacological activation of Liver X Receptor (LXR) has been shown to increase expression of ApoE and ABCA1 proteins, reducing neurodegeneration in murine models of Alzheimer’s disease. Because previous reports determined that Nectandra reticulata (Lauraceae) extract has agonistic LXRs activity, the objective of this study was to determine the metabolites present in this extract and to evaluate their in silico and in vitro agonistic activity. The chromatographic analysis revealed the presence of three glycosylated flavonols. The in silico study showed that isolated flavonoids generate a hydrogen bond with T302 and T316 (LXRα and LXRβ, respectively). The in vitro study showed that the flavonoids increased the expression of mRNA of both APOE and ABCA1 target genes of LXRs, as observed by qRT-PCR. The bioactive flavonoids isolated in this study possess a documented antioxidant effect; when combined with their LXR agonist activity, they become promising bioactive candidates for use in nutraceutical formulations aimed at promoting brain health and anti-inflammatory effects.

Lipid metabolism is a vital biological process essential for human health, encompassing key pathways necessary for the survival and homeostasis of all organisms. Liver X Recep-tors (LXRs) are extensively acknowledged as pivotal regulators of lipid homeostasis and inflammatory responses. Pharmacological activation of liver X receptor (LXR) has been shown to increase expression of ApoE and ABCA1 reducing neurodegeneration in murine models of Alzheimer´s disease. Because previous reports determined that Nectandra reticu-lata (Lauraceae) extract has agonistic LXRs activity, the objective of this study was to de-termine the metabolites present in this extract and to evaluate their in silico and in vitro agonistic activity. Identification was done by reversed phase (RP) ultra-high performance liquid chromatography (UHPLC) with a diode array detector (DAD) and high resolution mass spectrometry with electrospray ionization (ESI-HR-MS). In silico study was performed by Auto Dock Vina. The in vitro agonist activity was evaluated using real-time re-verse transcription-polymerase chain reaction (qRT-PCR) to determine the RNA expression of ApoE and ABCA1. The chromatographic analysis revealed the presence of three glycosylated flavonols: The in silico study showed that isolated flavonoids generate a hydrogen bond with T302 and T316 (LXRα and LXRβ respectively). The in vitro study showed that the flavonoids increased the expression of mRNA of both APOE and ABCA1 target genes of LXRs, as observed by qRT-PCR. The bioactive flavonoids isolated in this study possess documented antioxidant effect, when combined with their LXR agonist activity, they become promising bioactive candidates for use in nutraceutical formulations aimed at promoting brain health and anti-inflammatory effects.

A versatile two-step environmentally friendly synthesis of imidazo[4,5,1- ij ]quinolines is described.

The ethanolic extract of Nectandra reticulata contains a high amount of quercetin-3-O-rhamnoside (quercitrin) that has exhibited a significant activity toward Alzheimer's disease, specifically with LXR receptors. In this work, a methodology was validated following the specifications of the International Conference of Harmonization in terms of linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy (recovery), repeatability (intra-assay), intermediate precision (intra-laboratory), reproducibility (inter-laboratory), robustness, and specificity. The effect of location (Oiba, Granada, and Chiquinquira) and the extraction method (percolation, maceration, and ultrasound-assisted extraction) towards the chromatographic profile and quercitrin recovery was studied. Furthermore, a Box–Behnken design was conducted to optimize quercitrin extraction and extraction yield by ultrasonic-assisted extraction. The chromatographic method was validated, with a linear range from 5 to 180 mg quercitrin per L, LOD 0.26 mg L⁻¹, and LOQ 0.86 mg L⁻¹. Accuracy [recovery of 93.8% (w/w)], repeatability (relative standard deviation, RSD, 3.3%), intermediate precision (RSD 5.4%), and reproducibility (RSD 1.4%) were within the acceptable values. The method was robust and specific, except for the variation in the formic acid concentration. The location had a greater influence than the extraction method towards both the chromatographic profile and quercitrin recovery. Quercitrin extraction was maximized at 60% (v/v) ethanol and 50 °C, independent of the solvent : material ratio used. The highest yield values were achieved at 60% (v/v) ethanol and 50 °C, with a solvent : material ratio of 40 mL g⁻¹.