Person:
Martín Carmona, María Antonia

First Name

María Antonia

Last Name

Martín Carmona

URI

https://hdl.handle.net/20.500.14352/77618

Affiliation

Universidad Complutense de Madrid

Faculty / Institute

Farmacia

Department

Química en Ciencias Farmacéuticas

Area

Química Analítica

Identifiers

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Now showing 1 - 10 of 13

Eco-friendly liquid chromatographic separations based on the use of cyclodextrins as mobile phase additives
(Green Chemistry, 2011) González Ruiz, Víctor; León Leal, Andrés Gerardo; Menéndez Ramos, José Carlos; Martín Carmona, María Antonia; Olives Barba, Ana Isabel
Acetonitrile and methanol are the most popular solvents employed in analytical HPLC, but they suffer from a number of drawbacks from the environmental point of view. Alternative, greener mobile phases employing methanol or the less toxic solvent ethanol as the sole organic solvent are proposed in this paper, and applied to the problem of the separation of b-carbolines on C18-stationary phases. The use of b-cyclodextrin (b-CD) and (2-hydroxypropyl)-b-cyclodextrin (HPb-CD) as mobile phase additives allowed us to increase the proportion of water in the mobile phases without loss in the resolution or efficiency of the separations, leading initially to a considerable reduction of the proportion of methanol in the mobile phase (from 70% to 50%) and at a later stage, to the development of a mobile phase containing only 30% of ethanol. The b-carboline–cyclodextrin association constants were determined by HPLC, and the inclusion complexes were also characterized by 1 H-NMR, 13C-NMR and 2D-ROESY experiments, and these studies were used to explain the chromatographic behaviour. The new chromatographic methodology developed was validated and applied to the quantitation of b-carboline derivatives in spiked human serum samples. For the extraction of b-carboline alkaloids from serum samples, liquid–liquid extraction (LLE) and solid-phase extraction (SPE) procedures were compared. It was concluded that the combination of a pre-treatment procedure (ionic exchange SPE) with a water-enriched chromatographic separation leads to a promising, environmentally friendly new methodology.
Bisavenathramide Analogues as Nrf2 Inductors and Neuroprotectors in In Vitro Models of Oxidative Stress and Hyperphosphorylation
(Antioxidants, 2021) Cores Esperón, Ángel; Abril Comesaña, Sheila; Michalska Dziama, Patrycja; Duarte, Pablo; Olives Barba, Ana Isabel; Martín Carmona, María Antonia; Villacampa Sanz, Mercedes; León Martínez, Rafael; Menéndez Ramos, José Carlos
Oxidative stress is crucial to the outbreak and advancement of neurodegenerative diseases and is a common factor to many of them. We describe the synthesis of a library of derivatives of the 4-arylmethylen-2-pyrrolin-5-one framework by sequential application of a three-component reaction of primary amines, β-dicarbonyl compounds, and α-haloketones and a Knoevenagel condensation. These compounds can be viewed as cyclic amides of caffeic and ferulic acids, and are also structurally related to the bisavenanthramide family of natural antioxidants. Most members of the library showed low cytotoxicity and good activity as inductors of Nrf2, a transcription factor that acts as the master regulator of the antioxidant response associated with activation of the antioxidant response element (ARE). Nrf2-dependent protein expression was also proved by the significant increase in the levels of the HMOX1 and NQO1 proteins. Some compounds exerted neuroprotective properties in oxidative stress situations, such as rotenone/oligomycin-induced toxicity, and also against protein hyperphosphorylation induced by the phosphatase inhibitor okadaic acid. Compound 3i, which can be considered a good candidate for further hit-to-lead development against neurodegenerative diseases due to its well-balanced multitarget profile, was further characterized by proving its ability to reduce phosphorylated Tau levels.
Bifunctional carbazole derivatives for simultaneous therapy and fluorescence imaging in prion disease murine cell models
(European Journal of Medicinal Chemistry, 2022) Staderini, Matteo; Vanni, Silvia; Colini Baldeschi, Arianna; Zattoni, Marco; Celauro, Luigi; Ferracin, Chiara; Bistaffa, Edoardo; Moda, Fabio; Pérez, Daniel I.; Martínez, Ana; Martín Carmona, María Antonia; Martín Cámara, Olmo; Cores Esperón, Ángel; Bianchini, Giulia; Kammerer, Robert; Menéndez Ramos, José Carlos; Legname, Giuseppe; Bolognesi, Maria Laura
Prion diseases are characterized by the self-assembly of pathogenic misfolded scrapie isoforms (PrPSc) of the cellular prion protein (PrPC). In an effort to achieve a theranostic profile, symmetrical bifunctional carbazole derivatives were designed as fluorescent rigid analogues of GN8, a pharmacological chaperone that stabilizes the native PrPC conformation and prevents its pathogenic conversion. A focused library was synthesized via a four- step route, and a representative member was confirmed to have native fluorescence, including a band in the near- infrared region. After a cytotoxicity study, compounds were tested on the RML-infected ScGT1 neuronal cell line, by monitoring the levels of protease-resistant PrPSc. Small dialkylamino groups at the ends of the molecule were found to be optimal in terms of therapeutic index, and the bis-(dimethylaminoacetamido)carbazole derivative 2b was selected for further characterization. It showed activity in two cellClines infected with the mouse-adapted RML strain (ScGT1 and ScN2a). Unlike GN8, 2b did not affect PrP levels, which represents a potential advantage in terms of toxicity. Amyloid Seeding Assay (ASA) experiments showed the capacity of 2b to delay the aggregation of recombinant mouse PrP. Its ability to interfere with the amplification of the scrapie RML strain by Protein Misfolding Cyclic Amplification (PMCA) was shown to be higher than that of GN8, although 2b did not inhibit the amplification of human vCJD prion. Fluorescent staining of PrPSc aggregates by 2b was confirmed in living cells. 2b emerges as an initial hit compound for further medicinal chemistry optimization towards strain- independent anti-prion compounds.
Project number: 373
Ensayo de inmersión del alumnado en el modelo IMRyD a través de la solicitud de un proyecto de investigación en un entorno de simulación
(2023) Olives Barba, Ana Isabel; Caja López, María Del Mar; Coronel Gonzalo, Cristina; Gómez Gómez, Beatriz; López Ruiz, María Beatriz; Martín Carbajo, María Laura; Martín Carmona, María Antonia; Ortega Moreno, María; Rodrigo Martín, Rosa; Rodríguez Moreno, María del Pilar; Sanz Riomoros, Isabel; Urrestarazu Morocoima, José Antonio; Zapatero Martínez, María
Se ha desarrollado una actividad combinada de Aprendizaje Basado en Proyectos (ABP) y Aprendizaje Basado en Simulación (ABS) durante el primer semestre del curso 2022-23, dentro de la asignatura obligatoria de Química Analítica II, que se imparte en el segundo curso del Grado en Farmacia y del Doble Grado en Farmacia y Nutrición Humana y Dietética de la UCM. Según la metodología propuesta, los estudiantes partieron de la idea de desarrollar un nuevo método analítico para cuantificar un compuesto de su interés presente en muestras alimentarias, farmacéuticas, clínicas o ambientales. Para ello, elaboraron una propuesta y solicitaron un proyecto de investigación en una convocatoria simulada que lanzaron los profesores en el campus virtual de la asignatura. Al final del semestre, se celebró una sesión de pósteres en la que se invitó a los estudiantes a presentar su trabajo, de forma similar a un congreso. El objetivo principal de la actividad ha sido familiarizar a los estudiantes con el formato habitual de los documentos científicos (IMRD), concienciarles sobre cómo elaborar una propuesta con soporte bibliográfico y desarrollar habilidades de comunicación oral y escrita que necesitarán en su desarrollo profesional y, en un futuro próximo, en la elaboración de sus TFGs y TFMs. La actividad se diseñó como una tarea complementaria al programa de la asignatura. Participaron voluntariamente en la actividad 46 estudiantes de dos grupos de la asignatura (45%) y se presentaron 13 propuestas. La presentación de los carteles y la sesión informativa fueron especialmente participativas y brindaron a los estudiantes la oportunidad de desarrollar un pensamiento crítico al juzgar los pósteres. Los profesores valoraron la actividad como una herramienta prometedora para el desarrollo competencial de los estudiantes, que anima al profesorado como diseñadores de entornos de aprendizaje activo.
An Easily Built Smoking Machine for Use by Undergraduate Students in the Determination of Total Particulate Matter and Nicotine in Tobacco Smoke
(Journal of Chemical Education, 2012) González Ruiz, Víctor; Martín Carmona, María Antonia; Olives Barba, Ana Isabel
Sampling mainstream cigarette smoke is a challenging and stimulating laboratory activity for undergraduate students. In addition to the public health significance, cigarette smoke is an unusual source of analytes to examine the differences between gaseous matrices versus liquid or solid matrices. Sophisticated automated smoking machines complying with international standards are not affordable for educational purposes. However, a less expensive and simple smoking apparatus can be easily built in any laboratory that yields reproducible smoking conditions and allows several cigarettes to be smoked simultaneously. We describe the construction of such an apparatus utilizing a solid-phase extraction manifold and chamber, and how it can be used by undergraduate students to generate cigarette smoke and trap the total particulate matter (TPM). The TPM can be later gravimetrically quantified and eluted with 2-propanol containing an internal standard to quantify th nicotine content. Because a set of six cigarettes can be “smoked” simultaneously, the proposed procedure allows the comparison of TPM and nicotine content in mainstream smoke from normal and light cigarettes
A down-scaled fluorimetric determination of the solubility properties of drugs to minimize waste generation
(Green Chemistry, 2013) González Ruiz, Víctor; Olives Barba, Ana Isabel; Martín Carmona, María Antonia
A miniaturized fluorescence assay on multi-well plates has been developed to study the solubility enhancement effect of (2-hydroxypropyl)-β-cyclodextrin on three anti-tumor alkaloids. The measurement of the fluorescence emission on a multi-well plate format has been proved to be a rapid and efficient technique to evaluate the solubility of pharmaceutical formulations of new drugs that help save time, reagents and wastes in the search for greener analytical strategies. The proposed methodology was compared with a reference HPLC solubility study and was employed to examine the enhancement of the solubility of camptothecin, luotonin A, and a synthetic derivative of the latter in the presence of (2-hydroxypropyl)-β-cyclodextrin. Considerable reductions in the time of analysis (almost 50 times faster) and the volume of organic solvents employed (close to 25 times less acetonitrile needed) were achieved. The nature of the inclusion complexes was investigated by analysis of the phase-solubility diagrams obtained by the newly developed method and was complemented with spectrofluorimetry and ESI-MS experiments. The concentrations of solubilised compounds found by both methodologies were in good agreement (R2 > 0.98). The analytical figures of merit of both methodologies were compared and the adequacy of the proposed method for the development of drug solubilisation studies was discussed.s.
Fluorescence properties of the anti-tumour alkaloid luotonin A and new synthetic analogues: pH modulation as an approach to their fluorimetric quantitation in biological samples
(Journal of Luminescence, 2012) González Ruiz, Víctor; González-Cuevas, Yamisley; Arunachalam, Sankaralingam; Martín Carmona, María Antonia; Olives Barba, Ana Isabel; Ribelles, Pascual; Ramos García, María Teresa; Menéndez Ramos, José Carlos
Luotonin A is an alkaloid structurally related to the natural anti-tumour agent camptothecin. The fluorescence behaviour of luotonin A and a series of six analogues is described in the present work. The influence of solvent polarity and pH on the native fluorescence properties of these alkaloids was studied, finding that in organic solvents or in aqueous solutions (pH 5.5–7.2) the neutral form of the luotonin derivatives emit in the region of 410–450 nm but, in both media, acidification to pH values below 3.0 causes a new emission band to appear at about 500 nm. An ESPT reaction occurs due to the protonation of the basic nitrogen atoms of the pentacyclic ring. Acid-base titrations of luotonin A and its derivatives in aqueous and acetonitrile media were carried out in order to determine their pKa n values which were around 2, showing these compounds to be very weak bases. In aqueous media, the absence of an iso-emissive point in the emission spectra suggests the existence of more than two species in the proton transfer equilibria. The basicity of the luotonin A derivatives is increased in organic media, and a good correlation between the pKa n values and the chemical structure was found. The protonation of luotonin A was also studied by 1 H-NMR and 13C-NMR experiments, which proved the protonation of the nitrogen atoms at the positions 5 and 6 of the pentacyclic ring. The fluorescence quantum yields were determined in ethanol and in aqueous solutions under neutral and acidic conditions. The fluorescence quantum yields were higher in water for the case of the more polar compounds, and the opposite result was obtained for the more hydrophobic ones. The remarkable and interesting fluorescence properties of luotonin A prompted the development of its fluorimetric analytical quantitation, obtaining very good analytical features
SPE/RP-HPLC using C1 columns: an environmentally friendly alternative to conventional reverse-phase separations for quantitation of beta-carboline alkaloids in human serum samples
(Analytical and Bioanalytical Chemistry, 2010) González-Ruiz, Víctor; Olives Barba, Ana Isabel; Martín Carmona, María Antonia
Liquid chromatographic analysis of the anticancer alkaloid luotonin A and some new derivatives in human serum samples
(Journal of Separation Science, 2010) González Ruiz, Víctor; Mussardo, Pierluigi; Corda, Elisa; Girotti, Stefano; Olives Barba, Ana Isabel; Martín Carmona, María Antonia
The quantitation of the natural cytotoxic and anti‐inflammatory alkaloid luotonin A and five recently synthesized derivatives is described, constituting the first report of a HPLC method for the analysis of these compounds in human serum samples. The conditions for the chromatographic separation were optimized and the method was validated for the analysis of these compounds in biological samples according to international guidelines. An RP‐HPLC method with fluorimetric detection and a C 18 stationary phase was applied. Different ACN/water mobile phases were assayed, including 0–4% of a mobile phase modifier such as tetrahydrofuran, dioxane or tert‐butyl methyl ether. Isocratic and gradient elution conditions are compared. The influence of pH on the efficiency and resolution of the separation was also considered. The developed method was applied to the determination of luotonins in pooled human serum samples by gradient elution RP‐HPLC using a simple cleanup procedure. The proposed chromatographic method exhibits satisfactory analytical figures of merit, with LOD from 1.0×10−10 to 2.0×10−10 M, intraday and interday precision below 6% except for the concentration level closest to LOD, and good agreement between experimental and theoretical concentrations. Therefore, the developed method is suitable, reliable, rapid, and simple.
A fluorescent styrylquinoline with combined therapeutic and diagnostic activities against alzheimer’s and prion diseases
(ACS Medicinal Chemistry Letters, 2013) Staderini, Matteo; Aulić, Suzana; Bartolini, Manuela; Tran, Hoang Ngoc Ai; González-Ruiz, Víctor; Pérez, Daniel I.; Martínez Gil, Ana; Andrisano, Vincenza; Legname, Giuseppe; Menéndez Ramos, José Carlos; Bolognesi, Maria Laura; Cabezas Baudot, Nieves; Martín Carmona, María Antonia
(E)-6-Methyl-4′-amino-2-styrylquinoline (3) is a small molecule with the proper features to potentially diagnose, deliver therapy and monitor response to therapy in protein misfolding diseases. These features include compound fluorescent emission in the NIR region and its ability to interact with both Aβ and prion fibrils, staining them with high selectivity. Styrylquinoline 3 also inhibits Aβ self-aggregation in vitro and prion replication in the submicromolar range in a cellular context. Furthermore, it is not toxic and is able to cross the blood brain barrier in vitro (PAMPA test).