Detalle Profesor

Nuestros investigadores
Carlos Aydillo Miguel
Publicaciones científicas más recientes (desde 2010)
01
Autores: Martín Escolano, R., (Autor de correspondencia); Molina Carreño, D.; Plano Amatriain, Daniel; et al.
Revista: PHARMACEUTICALS
ISSN   1424-8247  Vol.   14    5  2021  págs.   419
Chagas disease is usually caused by tropical infection with the insect-transmitted protozoan Trypanosoma cruzi. Currently, Chagas disease is a major public health concern worldwide due to globalization, and there are no treatments neither vaccines because of the long-term nature of the disease and its complex pathology. Current treatments are limited to two obsolete drugs, benznidazole and nifurtimox, which lead to serious drawbacks. Taking into account the urgent need for strict research efforts to find new therapies, here, we describe the in vitro and in vivo trypanocidal activity of a library of selected forty-eight selenocyanate and diselenide derivatives that exhibited leishmanicidal properties. The inclusion of selenium, an essential trace element, was due to the wellknown extensive pharmacological activities for selenium compounds including parasitic diseases as T. cruzi. Here we present compound 8 as a potential compound that exhibits a better profile than benznidazole both in vitro and in vivo. It shows a fast-acting behaviour that could be attributed to its mode of action: it acts in a mitochondrion-dependent manner, causing cell death by bioenergetic collapse. This finding provides a step forward for the development of a new antichagasic agent
02
Autores: Etxebeste Mitxeltorena, Mikel; Plano Amatriain, Daniel; Astráin Redín, Nora; et al.
Revista: ANTIOXIDANTS
ISSN   2076-3921  Vol.   10    4  2021  págs.   590
Breast cancer is a multifactor disease, and many drug combination therapies are applied for its treatment. Selenium derivatives represent a promising potential anti-breast cancer treatment. This study reports the cytotoxic activity of forty-one amides and phosphoramidates containing selenium against five cancer cell lines (MCF-7, CCRF-CEM, HT-29, HTB-54 and PC-3) and two nonmalignant cell lines (184B5 and BEAS-2B). MCF-7 cells were the most sensitive and the selenoamides I.1f and I.2f and the selenium phosphoramidate II.2d, with GI50 values ranging from 0.08 to 0.93 mu M, were chosen for further studies. Additionally, radical scavenging activity for all the compounds was determined using DPPH and ABTS colorimetric assays. Phosphoramidates turned out to be inactive as radical scavengers. No correlation was observed for the antioxidant activity and the cytotoxic effect, except for compounds I.1e and I.2f, which showed dual antioxidant and antitumor activity. The type of programmed cell death and cell cycle arrest were determined, and the results provided evidence that I.1f and I.2f induced cell death via autophagy, while the derivative II.2d provoked apoptosis. In addition, Western blot analysis corroborated these mechanisms with an increase in Beclin1 and LC3-IIB and reduced SQSTM1/p62 levels for I.1f and I.2f, as well as an increase in BAX, p21 and p53 accompanied by a decrease in BCL-2 levels for derivative II.2d.
03
Autores: Etxebeste Mitxeltorena, Mikel; Plano Amatriain, Daniel; Espuelas Millán, María Socorro; et al.
Revista: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN   0066-4804  Vol.   65    1  2021  págs.   e00524-20
Two new series of 28 selenocyanate and diselenide derivatives containing amide moieties were designed, synthesized, and evaluated for their leishmanicidal activity against Leishmania infantum axenic amastigotes, and selectivity was assessed in human THP-1 cells. Eleven compounds exhibited excellent leishmanicidal activity with EC50 values lower than the reference drug miltefosine (EC50 = 2.84 mu M). In addition, for six of them the selectivity index ranged from 9 to >1,442, greater than both references used. The most potent and selective compounds were compounds 2h, 2k, and 2m that displayed EC50 values of 0.52, 1.19, and 0.50 mu M, respectively, and a high selectivity index (SI) when tested against THP-1 monocytic cells (SI = >1,442, >672, and >1,100, respectively). These derivatives showed an efficacy similar to that of the reference drugs but much better SI values. They also showed interesting activity values against infected macrophages. Trypanothione reductase (TryR) activity and intracellular thiol level measurement assays were performed for the three best compounds in an attempt to elucidate their mechanism of action. Despite that the new analogs exhibited comparable or better inhibitory activities than the reference TryR inhibitors, more studies are necessary to confirm this result. In summary, our findings suggest that the three compounds described here could constitute leading leishmanicidal drug candidates.
04
Autores: Etxebeste Mitxeltorena, Mikel; Plano Amatriain, Daniel; Espuelas Millán, María Socorro; et al.
Revista: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN   0066-4804  Vol.   65    10  2021  págs.   e00590-21
This work reports the synthesis and characterization by Fourier transform infrared spectroscopy (FTIR), H-1, C-13, and Se-79 nuclear magnetic resonance (NMR), mass spectrometry, and elemental analysis techniques as well as the in vitro evaluation of the leishmanicidal activity of 13 new selenophosphoramidate derivatives. Among the new compounds, four of them (compounds 1f, 1g, 2f, and 2g), which exhibited the best profiles, were tested against infected macrophages and were selected for further studies related to their leishmanicidal mechanism. In this regard, trypanothione redox system alteration was determined. Compound 1g, under similar conditions, was more effective than the corresponding references. In addition, theoretical calculations showed that this compound also presents most physicochemical and pharmacokinetic properties within the ranges expected for orally available drugs. It is believed that selenophosphoramidate functionalities may represent a scaffold to be explored toward the development of new agents for leishmania treatment.
05
Autores: Puig Rigall, Joan; Blanco Prieto, María; Aydillo Miguel, Carlos; et al.
Revista: JOURNAL OF MOLECULAR LIQUIDS
ISSN   0167-7322  Vol.   324  2021 
The combination of polymeric surfactants with different features into mixed micelles give access to properties that may be superior to the single-component micelles. In this work, we investigated synergistic effects in mixtures of D-alpha-Tocopheryl polyethylene glycol succinate (TPGS) with poloxamines (also known as Tetronic), pH-responsive and thermogelling polyethylene oxide (PEO)-polypropylene oxide (PPO) 4-arm block copolymers. We examined the morphology of the self-assembled micelles of TPGS with Tetronic 1107 (T1107) and 908 (T908) in the presence of naproxen (NA), used as a model drug, and assessed the capacity of the single and mixed micelles to trap the guest, using a combination of small-angle neutron scattering (SANS) and NMR spectroscopy (1D, 2D-NOESY and diffusion NMR), over a range of compositions and temperatures, in the dilute regime and gel state. NA did not interact with T1107 or T908 in their unimer form, but it was incorporated into the hydrophobic core of the micelles above the critical micellar temperature (CMT). In contrast, TPGS dissolved NA at any temperature, mainly in the tocopherol core, with some partitioning in the PEG-shell. The micellar structure was not altered by the presence of NA, except for an expansion of the core size, a result of the preferential accumulation of NA in that compartment. The solubility of the drug in single component micelles increased markedly with temperature, while mixed micelles produced an intermediate enhancement o
06
Autores: Ruberte Sánchez, Ana Carolina; Sanmartín Grijalba, Carmen; Aydillo Miguel, Carlos; et al.
Revista: JOURNAL OF MEDICINAL CHEMISTRY
ISSN   0022-2623  Vol.   63    4  2020  págs.   1473 - 1489
Incorporation of selenium (Se) atom into small molecules can substantially enhance their antioxidant, anti-inflammatory, antimutagenic, antitumoral or chemopreventive, antiviral, antibacterial, antifungal, antiparasitic, and neuroprotective effects. Specifically, selenazo compounds have received great attention owing to their chemical properties, pharmaceutical applications, and low toxicity. In this Perspective, we compile extensive literature evidence with the description and discussion of the most recent advances in different selenazo and selenadiazo motifs as potential pharmacological candidates. We also provide some perspectives on the challenges and future directions in the advancement of these selenazo compounds, each of which could generate drug candidates for various diseases.
07
Autores: Ruberte, A. C.; González Gaitano, Gustavo; Sharma, A. K.; et al.
Revista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN   1422-0067  Vol.   23  2020  págs.   9017
Aspirin (ASA) has attracted wide interest of numerous scientists worldwide thanks to its chemopreventive and chemotherapeutic effects, particularly in colorectal cancer (CRC). Incorporation of selenium (Se) atom into ASA has greatly increased their anti-tumoral efficacy in CRC compared with the organic counterparts without the Se functionality, such as the promising antitumoral methylseleno-ASA analog (1a). Nevertheless, the efficacy of compound 1a in cancer cells is compromised due to its poor solubility and volatile nature. Thus, 1a has been formulated with native alpha-, beta- and gamma-cyclodextrin (CD), a modified beta-CD (hydroxypropyl beta-CD, HP-beta-CD) and Pluronic F127, all of them non-toxic, biodegradable and FDA approved. Water solubility of 1a is enhanced with beta- and HP- beta-CDs and Pluronic F127. Compound 1a forms inclusion complexes with the CDs and was incorporated in the hydrophobic core of the F127 micelles. Herein, we evaluated the cytotoxic potential of 1a, alone or formulated with beta- and HP- beta-CDs or Pluronic F127, against CRC cells. Remarkably, 1a formulations demonstrated more sustained antitumoral activity toward CRC cells. Hence, beta-CD, HP-beta-CD and Pluronic F127 might be excellent vehicles to improve pharmacological properties of organoselenium compounds with solubility issues and volatile nature.
08
Autores: Ruberte Sánchez, Ana Carolina; Ramos Inza, Sandra; Aydillo Miguel, Carlos; et al.
Revista: ANTIOXIDANTS
ISSN   2076-3921  Vol.   9    1  2020  págs.   55
Selenium compounds are pivotal in medicinal chemistry for their antitumoral and antioxidant properties. Forty seven acylselenoureas have been designed and synthesized following a fragment-based approach. Different scaffolds, including carbo- and hetero-cycles, along with mono- and bi-cyclic moieties, have been linked to the selenium containing skeleton. The dose- and time-dependent radical scavenging activity for all of the compounds were assessed using the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2 '-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. Some of them showed a greater radical scavenging capacity at low doses and shorter times than ascorbic acid. Therefore, four compounds were evaluated to test their protective effects against H2O2-induced oxidative stress. One derivative protected cells against H2O2-induced damage, increasing cell survival by up to 3.6-fold. Additionally, in vitro cytotoxic activity of all compounds was screened against several cancer cells. Eight compounds were selected to determine their half maximal inhibitory concentration (IC50) values towards breast and lung cancer cells, along with their selectivity indexes. The breast cancer cells turned out to be much more sensitive than the lung. Two compounds (5d and 10a) stood out with IC50 values between 4.2 mu M and 8.0 mu M towards MCF-7 and T47D cells, with selectivity indexes greater than 22.9. In addition, compound 10b exhibited dual antioxidant and cytotoxic activities. Although further evidence is needed, the acylselenourea scaffold could be a feasible frame to develop new dual agents.
09
Autores: Ruberte Sánchez, Ana Carolina; Aydillo Miguel, Carlos; Sharma, A. K.; et al.
Revista: RSC ADVANCES
ISSN   2046-2069  Vol.   10    63  2020  págs.   38404 - 38408
An effective and straightforward synthesis of 3-seleno functionalized indolinone (5) involving Vilsmeier reagent is presented. Likewise, a procedure to achieve lactamization of diclofenac with excellent yields by using hydrides is also ascertained. Compound 5 exhibited impressive growth inhibition in most of the cell lines in an NCI-60 panel, particularly towards resistant breast cancer cells.
10
Autores: Aydillo Miguel, Carlos; Mazo, Nuria; Navo, Claudio Daniel; et al.
Revista: CHEMBIOCHEM
ISSN   1439-4227  Vol.   20    10  2019  págs.   1246 - 1250
11
Autores: Díaz Hernando, Marta; de Lucio, H. ; Moreno Amatria, Esther; et al.
Revista: ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
ISSN   0066-4804  Vol.   63    5  2019  págs.   e02200-18
A novel series of thirty-one N-substituted urea, thiourea, and selenourea derivatives containing diphenyldiselenide entities were synthesized, fully characterized by spectroscopic and analytical methods, and screened for their in vitro leishmanicidal activities. The cytotoxic activity of these derivatives was tested against Leishmania infantum axenic amastigotes, and selectivity was assessed in human THP-1 cells. Thirteen of the synthesized compounds showed a significant antileishmanial activity, with 50% effective concentration (EC50) values lower than that for the reference drug miltefosine (EC50, 2.84 mu M). In addition, the derivatives 9, 11, 42, and 47, with EC50 between 1.1 and 1.95 mu M, also displayed excellent selectivity (selectivity index ranged from 12.4 to 22.7) and were tested against infected macrophages. Compound 11, a derivative with a cyclohexyl chain, exhibited the highest activity against intracellular amastigotes, with EC50 values similar to those observed for the standard drug edelfosine. Structure-activity relationship analyses revealed that N-aliphatic substitution in urea and selenourea is recommended for the leish-manicidal activity of these analogs. Preliminary studies of the mechanism of action for the hit compounds was carried out by measuring their ability to inhibit trypanothione reductase. Even though the obtained results suggest that this enzyme is not the target for most of these derivatives, their activity comparable to that of the standards
12
Autores: Ruberte Sánchez, Ana Carolina; Plano Amatriain, Daniel; Encio, I.; et al.
Revista: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN   0223-5234  Vol.   157  2018  págs.   14 - 27
Twenty-seven novel benzo[c][1,2,5]selenadiazole-5-carboxylic acid (BSCA) derivatives were designed and synthesized. Anti-proliferative activity of these structures was tested in vitro against a panel of five human cancer cell lines, including prostate (PC-3), colon (HT-29), leukemia (CCRF-CEM), lung (HTB-54) and breast (MCF-7). Four compounds (5, 6, 7 and 19) showed potent inhibitory activity with GI(50) values below 10 mu M in at least one of the cancer cell lines. The selectivity of these compounds was further examined in two non-malignant cell lines derived from breast (18465) and lung (BEAS-2B). Compound 7 exhibited promising anti-proliferative activity (GI(50) = 3.7 mu M) in MCF-7 cells, together with high selectivity index (SI> 27.1). The induction of cell death by compound 7 was independent of the apoptotic process and it did not affect cell cycle progression either. Likewise, radical scavenging properties of the new selenadiazole derivatives were confirmed by testing their ability to scavenge DPPH radicals. Four compounds (1, 2, 8 and 9) showed potent radical scavenging activity, compound 9 being the most effective. Overall, while compound 7 was identified as the most cell growth inhibitory agent and selectively toxic to cancer cells, compound 9 proved to be the most potent antioxidant among the selenadiazole derivatives synthesized. This series of compounds can serve as an excellent scaffold to achieve new and potent antioxidant compounds useful for several diseases, i.e. cancer, neurodegenerative, heart diseases and leishmaniasis, considering the high radical scavenging activity and low toxicity showed by most of the compounds. (C) 2018 Elsevier Masson SAS. All rights reserved.
13
Autores: Gutiérrez Jiménez, Marta Isabel; Aydillo Miguel, Carlos; Navo Nájera, Claudio Daniel; et al.
Revista: ORGANIC LETTERS
ISSN   1523-7060  Vol.   18    12  2016  págs.   2796-2799
14
Autores: Rojas Ocáriz, Víctor; Compañón Pérez, Ismael; Aydillo Miguel, Carlos; et al.
Revista: JOURNAL OF ORGANIC CHEMISTRY
ISSN   0022-3263  Vol.   81    14  2016  págs.   5929-5941
15
Autores: Jiménez Osés, Gonzalo (Autor de correspondencia); Aydillo Miguel, Carlos; Busto Sancirián, Jesús Hector; et al.
Revista: JOURNAL OF ORGANIC CHEMISTRY
ISSN   0022-3263  Vol.   79    6  2014  págs.   2556-2563
16
Autores: Aydillo Miguel, Carlos; Compañón Pérez, Ismael; Avenoza Aznar, Alberto (Autor de correspondencia); et al.
Revista: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN   0002-7863  Vol.   136    2  2014  págs.   789-800
17
Autores: Aydillo Miguel, Carlos; Navo Nájera, Claudio Daniel; Busto Sancirián, Jesús Hector; et al.
Revista: JOURNAL OF ORGANIC CHEMISTRY
ISSN   0022-3263  Vol.   78    21  2013  págs.   10968-10977
18
Autores: Aydillo Miguel, Carlos; Avenoza Aznar, Alberto (Autor de correspondencia); Busto, Jesús H.; et al.
Revista: ORGANIC LETTERS
ISSN   1523-7060  Vol.   14    1  2012  págs.   334-337
19
Autores: Aydillo Miguel, Carlos; Jiménez Osés, Gonzalo; Avenoza Aznar, Alberto (Autor de correspondencia); et al.
Revista: JOURNAL OF ORGANIC CHEMISTRY
ISSN   0022-3263  Vol.   76    17  2011  págs.   6990-6996
01
Autores: Ramos Inza, Sandra; Aydillo Miguel, Carlos; Sanmartín Grijalba, Carmen; et al.
Libro: Heterocycles - Synthesis and Biological Activities
2019  págs.   1 - 21