Person: Martín Cámara, Olmo
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First Name
Olmo
Last Name
Martín Cámara
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
- Project number: 263
Item Aprendizaje de las prácticas de laboratorio de Química Farmacéutica del Grado en Farmacia y Doble Grado en Farmacia y Nutrición a través del aula virtual(2022) Menéndez Ramos, José Carlos; Hernáiz Gómez-Dégano, María José; Pedregal Freire, Carmen; Cabezas Baudot, Nieves; Villacampa Sanz, Mercedes; Campo Pérez, Carmen Luisa del; Salazar Martínez de Pisón, María Loreto; González Matilla, Juan Francisco; Hoyos Vidal, Pilar; Esteban García, Gemma; Martín Martín, Antonio; Rico Arjona, Rocío; Gómez-Carpintero Jiménez, Jorge; Martín Cámara, Olmo; Cores Esperón, Ángel Item 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 LauraPrion 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.Item Curcumin-Piperlongumine Hybrids with a Multitarget Profile Elicit Neuroprotection in In Vitro Models of Oxidative Stress and Hyperphosphorylation(Antioxidants, 2021) Cores Esperón, Ángel; Carmona Zafra, Noelia; Martín Cámara, Olmo; Sánchez Cebrián, Juan Domingo; Duarte, Pablo; Villacampa Sanz, Mercedes; Bermejo Bescos, María De La Paloma; Martín-Aragón Álvarez, Sagrario; León Martínez, Rafael; Menéndez Ramos, José CarlosCurcumin shows a broad spectrum of activities of relevance in the treatment of Alzheimer’s disease (AD); however, it is poorly absorbed and is also chemically and metabolically unstable, leading to a very low oral bioavailability. A small library of hybrid compounds designed as curcumin analogues and incorporating the key structural fragment of piperlongumine, a natural neuroinflammation inhibitor, were synthesized by a two-step route that combines a three-component reaction between primary amines, β-ketoesters and α-haloesters and a base-promoted acylation with cinnamoyl chlorides. These compounds were predicted to have good oral absorption and CNS permeation, had good scavenging properties in the in vitro DPPH experiment and in a cellular assay based on the oxidation of dichlorofluorescin to a fluorescent species. The compounds showed low toxicity in two cellular models, were potent inductors of the Nrf2-ARE phase II antioxidant response, inhibited PHF6 peptide aggregation, closely related to Tau protein aggregation and were active against the LPS-induced inflammatory response. They also afforded neuroprotection against an oxidative insult induced by inhibition of the mitochondrial respiratory chain with the rotenone-oligomycin A combination and against Tau hyperphosphorylation induced by the phosphatase inhibitor okadaic acid. This multitarget pharmacological profile is highly promising in the development of treatments for AD and provides a good hit structure for future optimization efforts.Item Multitarget Hybrid Fasudil Derivatives as a New Approach to the Potential Treatment of Amyotrophic Lateral Sclerosis(Journal of Medicinal Chemistry, 2022) Martín Cámara, Olmo; Arribas Blázquez, Marina; Wells, Geoffrey; Morales-Tenorio, Marcos; Martin Requero, Ángeles; Porras, Gracia; Martínez, Ana; Giorgi, Giorgo; López-Alvarado Gutiérrez, María Pilar; Lastres Becker, Isabel; Menéndez Ramos, José CarlosHybrid compounds containing structural fragments of the Rho kinase inhibitor fasudil and the NRF2 inducers caffeic and ferulic acids were designed with the aid of docking and molecular mechanics studies. Following the synthesis of the compounds using a peptide-coupling methodology, they were characterized for their ROCK2 inhibition, radical scavenging, effects on cell viability (MTT assay), and NRF2 induction (luciferase assay). One of the compounds (1d) was selected in view of its good multitarget profile and good tolerability. It was able to induce the NRF2 signature, promoting the expression of the antioxidant response enzymes HO-1 and NQO1, via a KEAP1-dependent mechanism. Analysis of mRNA and protein levels of the NRF2 pathway showed that 1d induced the NRF2 signature in control and SOD1-ALS lymphoblasts but not in sALS, where it was already increased in the basal state. These results show the therapeutic potential of this compound, especially for ALS patients with a SOD1 mutation.Item Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation(Pharmaceutics, 2021) González Ruiz, Víctor; Cores Esperón, Ángel; Martín Cámara, Olmo; Serrano Orellana, Karen; Michalska Dziama, Patrycja; Cervera Carrascón, Víctor Enrique; León Martínez, Rafael; Olives Barba, Ana Isabel; Martín Carmona, María Antonia; Menéndez Ramos, José CarlosThe use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. These cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotometry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-β-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin.