Person: Menéndez Ramos, José Carlos
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First Name
José Carlos
Last Name
Menéndez Ramos
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Química en Ciencias Farmacéuticas
Area
Química Orgánica
Identifiers
12 results
Search Results
Now showing 1 - 10 of 12
Item An Expedient Regio- and Diastereoselective Synthesis of Hybrid Frameworks with Embedded Spiro[9,10]dihydroanthracene [9,3′]-pyrrolidine and Spiro[oxindole-3,2′-pyrrolidine] Motifs via an Ionic Liquid-Mediated Multicomponent Reaction(Molecules, 2015) Arumugam, Natarajan; Almansour, Abdulrahman; Kumar, Raju; Menéndez Ramos, José Carlos; Sultan, Mujeeb; Karama, Usama; Ghabbour, Hazem; Fun, Hoong-KunA series of hitherto unreported anthracene-embedded dispirooxindoles has been synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of an azomethine ylide, generated in situ from the reaction of isatin and sarcosine to 10-benzylideneanthracen9(10H)-one as a dipolarophile in 1-butyl-3-methylimidazolium bromide([bmim]Br), an ionic liquid. This reaction proceeded regio- and diastereoselectively, in good to excellent yields.Item ITH14001, a CGP37157-Nimodipine Hybrid Designed to Regulate Calcium Homeostasis and Oxidative Stress, Exerts Neuroprotection in Cerebral Ischemia(ACS Chemical Neuroscience, 2016) Buendia, Izaskun; Tenti, Giammarco; Michalska Dziama, Patrycja; Méndez-López, Iago; Luengo, Enrique; Satriani, Michele; Padín-Nogueira, Fernando; López, Manuela G.; Ramos García, María Teresa; García, Antonio G.; Menéndez Ramos, José Carlos; León Martínez, RafaelDuring brain ischemia, oxygen and glucose deprivation induces calcium overload, extensive oxidative stress, neuroinflammation, and, finally, massive neuronal loss. In the search of a neuroprotective compound to mitigate this neuronal loss, we have designed and synthesized a new multitarget hybrid (ITH14001) directed at the reduction of calcium overload by acting on two regulators of calcium homeostasis; the mitochondrial Na+/Ca2+ exchanger (mNCX) and L-type voltage dependent calcium channels (VDCCs). This compound is a hybrid of CGP37157 (mNCX inhibitor) and nimodipine (L-type VDCCs blocker), and its pharmacological evaluation revealed a moderate ability to selectively inhibit both targets. These activities conferred concentration-dependent neuroprotection in two models of Ca2+ overload, such as toxicity induced by high K+ in the SH-SY5Y cell line (60% protection at 30 μM) and veratridine in hippocampal slices (26% protection at 10 μM). It also showed neuroprotective effect against oxidative stress, an activity related to its nitrogen radical scavenger effect and moderate induction of the Nrf2-ARE pathway. Its Nrf2 induction capability was confirmed by the increase of the expression of the antioxidant and anti-inflammatory enzyme heme-oxygenase I (3-fold increase). In addition, the multitarget profile of ITH14001 led to anti-inflammatory properties, shown by the reduction of nitrites production induced by lipopolysaccharide in glial cultures. Finally, it showed protective effect in two acute models of cerebral ischemia in hippocampal slices, excitotoxicity induced by glutamate (31% protection at 10 μM) and oxygen and glucose deprivation (76% protection at 10 μM), reducing oxidative stress and iNOS deleterious induction. In conclusion, our hybrid derivative showed improved neuroprotective properties when compared to its parent compounds CGP37157 and nimodipine.Item Discovery of the first dual GSK3β inhibitor/Nrf2 inducer. A new multitarget therapeutic strategy for Alzheimer’s disease(Scientific Reports, 2017) Gameiro, Isabel; Michalska Dziama, Patrycja; Tenti, Giammarco; Cores Esperón, Ángel; Buendia, Izaskun; Rojo, Ana I.; Georgakopoulos, Nikolaos D.; López, Manuela G.; Hernández, Jesús M.; Ramos García, María Teresa; Wells, Geoffrey; Cuadrado, Antonio; Menéndez Ramos, José Carlos; León Martínez, RafaelThe formation of neurofibrillary tangles (NFTs), oxidative stress and neuroinflammation have emerged as key targets for the treatment of Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder. These pathological hallmarks are closely related to the over-activity of the enzyme GSK3β and the downregulation of the defense pathway Nrf2-EpRE observed in AD patients. Herein, we report the synthesis and pharmacological evaluation of a new family of multitarget 2,4-dihydropyrano[2,3-c]pyrazoles as dual GSK3β inhibitors and Nrf2 inducers. These compounds are able to inhibit GSK3β and induce the Nrf2 phase II antioxidant and anti-inflammatory pathway at micromolar concentrations, showing interesting structure-activity relationships. The association of both activities has resulted in a remarkable anti-inflammatory ability with an interesting neuroprotective profile on in vitro models of neuronal death induced by oxidative stress and energy depletion and AD. Furthermore, none of the compounds exhibited in vitro neurotoxicity or hepatotoxicity and hence they had improved safety profiles compared to the known electrophilic Nrf2 inducers. In conclusion, the combination of both activities in this family of multitarget compounds confers them a notable interest for the development of lead compounds for the treatment of AD.Item 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 IsabelAcetonitrile 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.Item 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 CarlosLuotonin 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 featuresItem 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).Item Multicomponent Domino Synthesis, Anticancer Activity and Molecular Modeling Simulation of Complex Dispirooxindolopyrrolidines(Molecules, 2018) Arumugam, Natarajan; Almansour, Abdulrahman I.; Suresh Kumar, Raju; Govindasami, Periyasami; Al-thamili, Dhaifallah; Krishnamoorthy, Rajapandian; Periasamy, Vaiyapuri Subbarayan; Alshatwi, Ali; Mahalingam, S. M.; Thangamani, Shankar; Menéndez Ramos, José CarlosA series of spirooxindolopyrrolidine fused N -styrylpiperidone heterocyclic hybrids has been synthesized in excellent yield via a domino multicomponent protocol that involves one-pot three component 1,3-dipolar cycloaddition and concomitant enamine reactions performed in an inexpensive ionic liquid, namely 1-butyl-3-methylimidazolium bromide ([bmim]Br). Compounds thus synthesized were evaluated for their cytotoxicity against U-937 tumor cells. Interestingly; compounds 5i and 5m exhibited a better cytotoxicity than the anticancer drug bleomycin. In ddition; the effect of the synthesized compounds on the nuclear morphology of U937 FaDu cells revealed that treatment with compounds 5a–m led to their apoptotic cell death.Item Ethyl 4,4''-Dibromo-5'-(butylamino)-2',6'-dinitro-[1,1':3',1''-terphenyl]-4'-carboxylate(Molbank, 2015) Rocchi, Damiano; González, Juan F.; Menéndez Ramos, José CarlosEthyl 4,4''-Dibromo-5'-(butylamino)-2',6'-dinitro-[1,1':3',1''-terphenyl]-4'- carboxylate (2) which is a m-terphenyl derivative containing an hexasubstituted, highly functionalized substituted benzene core, has been synthesized.Item A Sustainable Approach to the Stereoselective Synthesis of Diazaheptacyclic Cage Systems Based on a Multicomponent Strategy in an Ionic Liquid(Molecules, 2016) Suresh Kumar, Raju; Almansour, Abdulrahman; Arumugam, Natarajan; Altaf, Mohammad; Menéndez Ramos, José Carlos; Kumar, Raju; Osman, HasnahThe microwave-assisted three-component reactions of 3,5-bis(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones, acenaphthenequinone and cyclic α-amino acids in an ionic liquid, 1-butyl-3-methylimidazolium bromide, occurred through a domino sequence affording structurally intriguing diazaheptacyclic cage-like compounds in excellent yields.Item Montmorillonite Clay-Promoted, Solvent-Free Cross-Aldol Condensations under Focused Microwave Irradiation(Molecules, 2014) Rocchi, Damiano; González, Juan; Menéndez Ramos, José CarlosAn environmentally benign, clean and general protocol was developed for the synthesis of aryl and heteroaryl trans-chalcones. This method involved solvent-free reaction conditions under microwave irradiation in the presence of a clay-based catalyst, and afforded the target compounds in good yields and short reaction times. Furthermore, the same conditions allowed the synthesis of symmetrical, diarylmethylene-α,β-unsaturated ketones from aromatic aldehydes and ketones.