Multitarget anti-Alzheimer and chemotherapeutic compounds

Principal Investigator

Dr. Diego Muñoz-Torrero

Biography

Prof. Diego Muñoz-Torrero obtained a degree in Pharmacy at the University of Barcelona in 1989, where he performed a PhD in Pharmacy (1994, Medicinal Chemistry) under the supervision of Prof. Pelayo Camps. Thereafter, he spent 2 years at the Institut für Organische Chemie, Georg-August Universität in Göttingen, Germany, under the supervision of Prof. Reinhard Brückner. In 2001 he was appointed Associate Professor of Organic and Medicinal Chemistry at the Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona (UB) and since July 2022 he is Full Professor at the same department.

 

He was Vice-Dean of Research of the Faculty of Pharmacy and Food Sciences (UB) from November 2009 until March 2018. He is currently Head of the Laboratory of Medicinal Chemistry of his faculty and member of the Governing Board of the Institute of Biomedicine of the UB (IBUB-Drug and Target Discovery) since its founding in 2007.

He is a member of the Spanish Society of Medicinal Chemistry (SEQT) and the Spanish Royal Society of Chemistry (RSEQ), Organic Chemistry Division.

He has authored more than 110 papers, 10 patents, and 8 book chapters, and guest-edited 18 special issues in scientific journals (Molecules, Current Medicinal Chemistry, Current Pharmaceutical Design) on anti-Alzheimer and multitarget drugs and 9 E-books on recent advances in pharmaceutical sciences.

He currently serves as the Editor-in-Chief of the Medicinal Chemistry Section of the MDPI journal Molecules and belongs to the editorial advisory board of several medicinal chemistry journals.

 

Link to the Google Scholar Profile

 

Design and synthesis of novel disease-modifying anti-Alzheimer compounds

Healthy ageing is becoming increasingly threatened by a number of age-related neurodegenerative diseases, including Alzheimer’s disease (AD). AD causes loss of memory and other intellectual abilities, seriously interfering with daily life quality, and finally it inexorably causes the death of the patient. Over 46 million people are currently suffering AD and, unlike other major diseases whose mortality has significantly decreased in the past decade (i.e., breast or prostate cancer, heart disease, stroke or HIV), the number of AD-related deaths increased by 68%. Likewise, the economic burden associated to AD shows a clear rising trend, currently accounting for 1.1% of the global gross domestic product. These figures will rise in the upcoming years along with the increase in life expectancy, and hence in AD prevalence that might reach 75 million people by 2030 and 131 million by 2050, thereby posing a huge pressure on society and health systems.

The elusiveness of efficacious drugs against AD greatly accounts for its fatal consequences. So far, only five drugs have been approved for the palliative treatment of AD, whereas several drug candidates directed to β-amyloid (Aβ) peptide, thought to be the main culprit of the AD, have failed to show efficacy in advanced clinical trials. This has led to the credence that Aβ is just one of the causes of AD, which might involve a complex pathological network where several key targets are jointly responsible for the neurodegeneration. Accordingly, AD could be efficiently treated only through the simultaneous modulation of several key targets.

In our research group we are synthesizing novel anti-Alzheimer drug candidates, which have been rationally designed to hit multiple key biological targets involved in the pathological network of AD such as BACE-1, Aβ and tau aggregation, MAO-B, oxidative stress, soluble epoxide hydrolase and cholinesterases, among others.

Figure 1. Target combinations pursued in the multitarget anti-Alzheimer compounds developed in the period 1990-2020 (image from Pharmaceuticals 2022, 15, 545) and chemical structures and in vitro and in vivo biological profile of four multitarget anti-Alzheimer leads developed in our research group (images from J. Med. Chem. 2022, 65, 4909-4925, Eur. J. Med. Chem. 2021, 225, 113779, J. Med. Chem. 2021, 64, 812-839, and J. Med. Chem. 2020, 63, 9360-9390).

 

Design and synthesis of novel aminoquinoline chemotherapeutic agents

 

Human African Trypanosomiasis (HAT), caused by Trypanosoma brucei gambiense or T. brucei rhodesiense, and malaria, caused by Plasmodium species, are major protozoan parasitic diseases in developing countries, where they cause over 30,000 and 1-3 million deaths annually, respectively. Despite their mortality, conventional treatments are inadequate mainly due to toxicity issues and to the emergence of resistance, especially in the case of antimalarials such as chloroquine. In this light, there is a desperate need for new and better drugs.

Our work in this field focuses on the synthesis of several classes of antitrypanosomal aminoquinoline-based homo- and hetero-dimeric compounds, multicomponent reaction-based synthesis of quinoline-based derivatives with multi-trypanosomatid activity, and structure-based design of novel antimalarial glucose-6-phosphate dehydrogenase inhibitors.

Figure 2. Left: Structure and antitrypanosomal activity of the lead huprine and some homodimers, heterodimers, and side chain modified derivatives (image from Bioorg. Med. Chem. 2016, 24, 5162-5171). Right, up: Multicomponent reaction-based synthesis of multi-trypanosomatid quinoline derivatives (Eur. J. Med. Chem. 2015, 105, 120-137). Right, down: antimalarial glucose-6-phosphate dehydrogenase inhibitors designed from the first homology model of Plasmodium falciparum G6PD (Eur. J. Med. Chem. 2018, 146, 108-122).

Title of the project / contract: Development of a new generation of antimalarial drugs for the post-artemisinin era

Financing Firm/administration: Ministerio de Ciencia e Innovación (PDC2022-133085-I00)

Main researcher: Xavier Fernández Busquets

 

Title of the project / contract: Química mèdica i farmacologia de malalties neurodegeneratives/ Medicinal Chemistry and Pharmacology of Neurodegenerative Diseases

Financing Firm/administration: Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2021SGR357)

Main researcher: M. Carmen Escolano

 

Title of the project / contract: A novel class of compounds that block multiple early mechanisms of neurodegenerative diseases

Financing Firm/administration: Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2021 LLAV 00082)

Main researcher: Diego Muñoz-Torrero

 

Title of the project / contract: Síntesis de compuestos con mecanismos innovadores contra enfermedades neurodegenerativas y dolor neuropático

Financing Firm/administration: Ministerio de Ciencia, Innovación y Universidades / Agencia Estatal de Investigación / FEDER (PID2020-118127RB-I00)

Main researcher: Diego Muñoz-Torrero / Santiago Vázquez

 

Title of the project / contract: Novel dual acting compounds for the treatment of neurodegenerative disorders

Financing Firm/administration: Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR)  (2019 LLAV 00017)

Main researcher: Diego Muñoz-Torrero 

 

Title of the project / contract: Asesoramiento en temas de Química Orgánica

Financing Firm/administration: CIDQO 2012 S.L. (FBG309659)

Main researcher: Diego Muñoz-Torrero 

 

Title of the project / contract: Desarrollo de nuevas rutas de síntesis de intermedios y optimización de procesos de síntesis orgánica de intermedios y principios activos farmacéuticos

Financing Firm/administration: Medichem S.A. (FBG309659)

Main researcher: Diego Muñoz-Torrero 

 

Title of the project / contract: Síntesis de compuestos con mecanismos innovadores contra enfermedades neurodegenerativas

Financing Firm/administration: Ministerio de Economía y Competitividad (SAF2017-82771-R)

Main researcher: Diego Muñoz-Torrero / Santiago Vázquez 

 

Title of the project / contract: Química mèdica i farmacologia de malalties neurodegeneratives/ Medicinal Chemistry and Pharmacology of Neurodegenerative Diseases

Financing Firm/administration: Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2017SGR106)

Main researcher: Diego Muñoz-Torrero 

 

Title of the project / contract: Discovery of New Antiparasitic Agents 

Financing Firm/administration: UNIUN - Unión Iberoamericana de Universidades (83UIUBS) 

Main researcher: José Manuel Bautista (Universidad Complutense de Madrid, coordinator of the project); Francisco Javier Luque / Diego Muñoz-Torrero (coordinators of the University of Barcelona team) 

 

Title of the project / contract: Hybridmoleküle und Polypharmakologie für die Wirkstoffentdeckung und -enwiklung (Hybrid molecules and polypharmacology in drug discovery and development)

Financing Firm/administration: Deutsche Forschungsgemeinschaft (DFG)

 (DFG DE 1546/8-1)

Main researcher: Michael Decker (coordinator of the project and of the University of Würzburg team); Diego Muñoz-Torrero (coordinator of the University of Barcelona team); Maria Laura Bolognesi (coordinator of the University of Bologna team)

 

Title of the project / contract: Exploración de nuevas dianas y estrategias multidiana para el diseño de compuestos contra enfermedades infecciosas y prevalentes

Financing Firm/administration: Ministerio de Economía y Competitividad (SAF2014-57094-R)

Main researcher: F. Javier Luque / Diego Muñoz-Torrero

 

Title of the project / contract: Química Farmacéutica

Financing Firm/administration: Agència de Gestió d'Ajuts Universitaris i de Recerca. Generalitat de Catalunya. AGAUR (2014SGR52)

Main researcher: Diego Muñoz-Torrero

 

Title of the project / contract: Nuevos compuestos de potencial interés industrial

Financing Firm/administration: Comisión Interministerial de Ciencia y Tecnología, CICYT (CTQ2011-22433)

Main researcher: Pelayo Camps

 

Title of the project / contract: Fons Prova de Concepte FPC-2010-19

Financing Firm/administration: Fundació Bosch i Gimpera – Barcelona Knowledge Campus (BKC)

Main researcher: Diego Muñoz-Torrero

 

Title of the project / contract: Colaboración entre la UB y Genoma España para el desarrollo de compuestos modificadores de la enfermedad de Alzheimer así como las acciones de desarrollo, de explotación industrial y de comercialización de la patente ES201000016

Financing Firm/administration: Fundación para el desarrollo de la investigación en genómica y proteómica (Genoma España)

Main researcher: Diego Muñoz-Torrero

Muñoz-Torrero, D.; Schopfer, L. M.; Lockridge, O.

Chlorpyrifos oxon activates glutamate and lysine for protein cross-linking

Chem. Res. Toxicol. 2023, 36, 112–121. Open access article

 

Gandini, A.; Gonçalves, A. E.; Strocchi, S.; Albertini, C.; Janočková, J.; Tramarin, A.; Grifoni, D.; Poeta, E.; Soukup, O.; Muñoz-Torrero, D.; Monti, B.; Sabaté, R.; Bartolini, M.; Legname, G.; Bolognesi, M. L.

Discovery of dual Aβ/tau inhibitors and evaluation of their therapeutic effect on a Drosophila model of Alzheimer’s disease

ACS Chem. Neurosci. 2022, 13, 3314–3329. Open access article

 

Bouzón-Arnáiz, I.; Avalos-Padilla, Y.; Biosca, A.; Caño-Prades, O.; Román-Álamo, L.; Valle, J.; Andreu, D.; Moita, D.; Prudêncio, M.; Arce, E.M.; Muñoz-Torrero, D.; Fernàndez-Busquets, X.

The protein aggregation inhibitor YAT2150 has potent antimalarial activity in Plasmodium falciparum in vitro cultures

BMC Biology 2022, 20, 197. Open access article

 

Codony, S.; Pont, C.; Griñán-Ferré, C.; Di Pede-Mattatelli, A.; Calvó-Tusell, C.; Feixas, F.; Osuna, S.; Jarné-Ferrer, J.; Naldi, M.; Bartolini, M.; Loza, M. I.; Brea, J.; Pérez, B.; Bartra, C.; Sanfeliu, C.; Juárez-Jiménez, J.; Morisseau, C.; Hammock, B. D.; Pallàs, M.; Vázquez, S.; Muñoz-Torrero, D.

Discovery and in vivo proof of concept of a highly potent dual inhibitor of soluble epoxide hydrolase and acetylcholinesterase for the treatment of Alzheimer’s disease

J. Med. Chem. 2022, 65, 4909-4925. Open access article

 

Jarne-Ferrer, J.; Griñán-Ferré, C.; Bellver-Sanchis, A.; Vázquez, S.; Muñoz-Torrero, D.; Pallàs, M.

A combined chronic low-dose soluble epoxide hydrolase and acetylcholinesterase pharmacological inhibition promotes memory reinstatement in Alzheimer's disease mice models

Pharmaceuticals 2022, 15, 908. Open access article

 

Sampietro, A.; Pérez-Areales, F. J.; Martínez, P.; Arce, E. M.; Galdeano, C.; Muñoz-Torrero, D.

Unveiling the multitarget anti-Alzheimer drug discovery landscape: A bibliometric analysis

Pharmaceuticals 2022, 15, 545. Open access article

 

Chemat, F.; Cirillo, G.; Muñoz-Torrero, D.; Dembinski, R. (eds.)

Molecules in 2022 (Special issue, 12 papers)

Molecules 2022, 27. Open Access Issue

 

Pont, C.; Ginex, T.; Griñan-Ferre, C.; Scheiner, M.; Mattellone, A.; Martínez, N.; Arce, E.M.; Soriano-Fernandez, Y.; Naldi, M.; De Simone, A.; Barenys, M.; Gómez-Catalán, J.; Perez, B.; Sabate, R.; Andrisano, V.; Loza, M.I.; Brea, J.; Bartolini, M.; Bolognesi, M.L.; Decker, M.; Pallas, M.; Luque, F.J.; Muñoz-Torrero, D.

From virtual screening hits targeting a cryptic pocket in BACE-1 to a nontoxic brain permeable multitarget anti-Alzheimer lead with disease-modifying and cognition-enhancing effects

Eur. J. Med. Chem. 2021, 225, 113779. Open access article

 

Zambrano, P.; Suwalsky, M.; Jemiola-Rzeminska, M.; Gallardo-Nelson, M.J.; Strzalka, K.; Muñoz-Torrero, D.

Protective role of a donepezil-huprine hybrid against the beta-amyloid (1-42) effect on human erythrocytes

Int. J. Mol. Sci. 2021, 22, 9563. Open access article

 

García Palmer, H.; Puig Borreil, I.; Tabernero Caturla, J.; Galdeano Cantador, C.; Muñoz-Torrero López-Ibarra, D.; Barril Alonso, X.; Ruiz Carmona, S.

Compounds for use in the treatment of hyperproliferative disorders

Patent EP21382343.8             Date of priority: 2021

Main institution: Fundació Privada Institut d'Investigació Oncològica de Vall d'Hebron (VHIO) / Universitat de Barcelona / Fundació Institució Catalana de Recerca i Estudis Avançats (ICREA)

 

Fernàndez Busquets, X.; Biosca Romanillos, A.; Bouzón Arnáiz, I.; Muñoz-Torrero López-Ibarra, D.

Compounds for the treatment of malaria

Patent EP21382949.2             Date of priority: 2021

Main institution: Fundació Institut de Bioenginyeria de Catalunya (IBEC) / Fundació ISGlobal - Institut de Salut Global Barcelona / Universitat de Barcelona

 

Muñoz-Torrero, D.; Rapposelli, S.; Gütschow, M.; Matos, M.J.; de Sousa, M.E.; Saso, L. (eds.)

Molecules Medicinal Chemistry Reviews 2021 (Special issue, 34 papers)

Molecules 2021, 26-27. Open Access Issue

 

Muñoz-Torrero, D.; Osborn, H.; Doerksen, R.J.; Socorro, S.  (eds.)

Featured Papers in Medicinal Chemistry (Special issue, 25 papers)

Molecules 2021, 26-27. Open Access Issue

 

Giménez-Llort, L.; Santana-Santana, M.; Ratia, M.; Pérez, B.; Camps, P.; Muñoz-Torrero, D.; Badia, A.; Clos, M.V.

Clock/sleep-dependent learning and memory in male 3xTg-AD mice at advanced disease stages and extrinsic effects of huprine X and the novel multitarget agent AVCRI104P3

Brain Sci. 2021, 11, 426 Open access article

 

Muñoz-Torrero, D.

The cream of the crop of the Medicinal Chemistry section of Molecules - 2019

Molecules 2021, 26, 1053. Open access editorial

 

Viayna, E.; Coquelle, N.; Cieslikiewicz-Bouet, M.; Cisternas, P.; Oliva, C. A.; Sánchez-López, E.; Ettcheto, M.; Bartolini, M.; De Simone, A.; Ricchini, M.; Rendina, M.; Pons, M.; Firuzi, O.; Pérez, B.; Saso, L.; Andrisano, V.; Nachon, F.; Brazzolotto, X.; García, M. L.; Camins, A.; Silman, I.; Jean, L.; Inestrosa, N. C.; Colletier, J.-P.; Renard, P.-Y.; Muñoz-Torrero, D.

Discovery of a potent dual inhibitor of acetylcholinesterase and butyrylcholinesterase with antioxidant activity that alleviates Alzheimer-like pathology in old APP/PS1 mice

J. Med. Chem. 2021, 64, 812-839

 

Pérez-Areales, F. J.; Garrido, M.; Aso, E.; Bartolini, M.; De Simone, A.; Espargaró, A.; Ginex, T.; Sabate, R.; Pérez, B.; Andrisano, V.; Puigoriol-Illamola, D.; Pallàs, M.; Luque, F. J.; Loza, M. I.; Brea, J.; Ferrer, I.; Ciruela, F.; Messeguer, A.; Muñoz-Torrero, D.

Centrally active multitarget anti-Alzheimer agents derived from the antioxidant lead CR-6

J. Med. Chem. 2020, 63, 9360-9390

 

Guzman, L.; Besa, G.; Linares, D.; González, L.; Pont, C.; Bartolini, M.; Haigis, A.-C.; Legradi, J.; Muñoz-Torrero, D.; Gómez-Catalán, J.; Barenys, M.

Evaluation of the effects of acetylcholinesterase inhibitors in the zebrafish touch-evoked response: quantitative vs. qualitative assessment

Environ. Sci. Eur. 2020, 32, 145. Open access article

 

Muñoz-Torrero, D.; De Pascual-Teresa, B. (eds.)

25th Anniversary of Molecules - Recent advances in medicinal chemistry (Special issue, 28 papers)

Molecules 2020, 25-26. Open Access Issue

 

Muñoz-Torrero, D. (ed.)

Breakthroughs in medicinal chemistry: New targets and mechanisms, new drugs, new hopes - 2020 (Special issue, 10 papers)

Molecules 2020, 25. Open Access Issue

 

Chemad, F.; Muñoz-Torrero, D.; Quirino, J.P.; Gauld, J.; Soloshonok, V.A.; Dembinski, R.; McPhee, D.J.; Schmidt, T.J.; von Itzstein, M. (eds.)

Feature papers to celebrate Molecules reaches 20,000 articles milestone (Special issue, 15 papers)

Molecules 2020, 25. Open Access Issue

 

 

Gütschow, M.; Vanden Eynde, J. J.; Jampilek, J.; Kang, C.; Mangoni, A. A.; Fossa, P.; Karaman, R.; Trabocchi, A.; Scott, P. J. H.; Reynisson, J.; Rapposelli, S.; Galdiero, S.; Winum, J.-Y.; Brullo, C.; Prokai-Tatrai, K.; Sharma, A. K.; Schapira, M.; Azuma, Y.-T.; Cerchia, L.; Spetea, M.; Torri, G.; Collina, S.; Geronikaki, A.; García-Sosa, A. T.; Vasconcelos, M. H.; Sousa, M. E.; Kosalec, I.; Tuccinardi, T.; Duarte, I. F.; Salvador, J. A. R.; Bertinaria, M.; Pellecchia, M.; Amato, J.; Rastelli, G.; Gomes, P. A. C.; Guedes, R. C.; Sabatier, J.-M.; Estévez-Braun, A.; Pagano, B.; Mangani, S.; Ragno, R.; Kokotos, G.; Brindisi, M.; González, F. V.; Borges, F.; Miloso, M.; Rautio, J.; Muñoz-Torrero, D. Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–7

Molecules 2020, 25, 2968. Open access article

 

Pérez-Areales, F. J.; Turcu, A. L.; Barniol-Xicota, M.; Pont, C.; Pivetta, D.; Espargaró, A.; Bartolini, M.; De Simone, A.; Andrisano, V.; Pérez, B.; Sabate, R.; Sureda, F. X.; Vázquez, S.; Muñoz-Torrero, D.

A novel class of multitarget anti-Alzheimer benzohomoadamantane_chlorotacrine hybrids modulating cholinesterases and glutamate NMDA receptors

Eur. J. Med. Chem. 2019, 180, 613-626.

 

Vanden Eynde, J. J.; Mangoni, A. A.; Rautio, J.; Leprince, J.; Azuma, Y.-T.; García-Sosa, A. T.; Hulme, C.; Jampilek, J.; Karaman, R.; Li, W.; Gomes, P. A. C.; Hadjipavlou-Litina, D.; Capasso, R.; Geronikaki, A.; Cerchia, L.; Sabatier, J.-M.; Ragno, R.; Tuccinardi, T.; Trabocchi, A.; Winum, J.-Y.; Luque, F. J.; Prokai-Tatrai, K.; Spetea, M.; Gütschow, M.; Kosalec, I.; Guillou, C.; Vasconcelos, M. H.; Kokotos, G.; Rastelli, G.; de Sousa, M. E.; Manera, C.; Gemma, S.; Mangani, S.; Siciliano, C.; Galdiero, S.; Liu, H.; Scott, P. J. H.; de los Ríos, C.; Agrofoglio, L. A.; Collina, S.; Guedes, R. C.; Muñoz-Torrero, D.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes–6

Molecules 2019, 25, 119. Open access article

 

Mangoni, A. A.; Vanden Eynde, J. J.; Jampilek, J.; Hadjipavlou-Litina, D.; Liu, H.; Reynisson, J.; Sousa, M. E.; Gomes, P. A. C.; Prokai-Tatrai, K.; Tuccinardi, T.; Sabatier, J.-M.; Luque, F. J.; Rautio, J.; Karaman, R.; Vasconcelos, M. H.; Gemma, S.; Galdiero, S.; Hulme, C.; Collina, S.; Gütschow, M.; Kokotos, G.; Siciliano, C.; Capasso, R.; Agrofoglio, L. A.; Ragno, R.; Muñoz-Torrero, D.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-5

Molecules 2019, 24, 2415. Open access article

 

Muñoz-Torrero, D.; Vázquez, S.; Pont, C.; Codony, S

Multitarget compounds for the treatment of Alzheimer’s disease

Patent PCT/EP2020/057914 Date of priority: 2019

Main institution: Universitat de Barcelona

 

Muñoz-Torrero, D.; Lavilla, R.; Pérez-Areales, F.J.; Ghashghaei, O.

Multicomponent reactions: A mighty journey partner for infectious tropical disease drug discovery

In Annual Reports in Medicinal Chemistry: Medicinal Approaches to Malaria and Other Tropical Disease, Part 2 Volume 53; Chibale, K. (ed.); Elsevier, 2019, 181-217.

 

Pérez-Areales, F.J.; Muñoz-Torrero, D.

Development of hybrid compounds to tackle Alzheimer's disease

in  Recent Advances in Pharmaceutical Sciences VIII; Muñoz-Torrero, D.; Cajal, Y.; Llobet, J.M. (eds.); Transworld Research Network, 2019, chapter 3, pp. 43-58. Open access E-book chapter

 

Muñoz-Torrero, D.; Decker, M. (eds.)

Molecules against Alzheimer II (Special issue, 7 papers)

Molecules 2019, 23-24. Open Access Issue

 

Caballero, A. B.; Espargaró, A.; Pont, C.; Busquets, M. A.; Estelrich, J.; Muñoz-Torrero, D.; Gamez, P.; Sabate, R.

Bacterial inclusion bodies for anti-amyloid drug discovery: Current and future screening methods

Curr. Protein Pept. Sci. 2019, 20, 563-576.

 

Espargaró, A.; Pont, C.; Gamez, P.; Muñoz-Torrero, D.; Sabate, R.

Amyloid pan-inhibitors: One family of compounds to cope with all conformational diseases

ACS Chem. Neurosci. 2019, 10, 1311-1317.

 

Mangoni, A. A.; Guillou, C.; Vanden Eynde, J. J.; Hulme, C.; Jampilek, J.; Li, W.; Prokai-Tatrai, K.; Rautio, J.; Collina, S.; Tuccinardi, T.; Sousa, M. E.; Sabatier, J.-M.; Galdiero, S.; Karaman, R.; Kokotos, G.; Torri, G.; Luque, F. J.; Vasconcelos, M. H.; Hadjipavlou-Litina, D.; Siciliano, C.; Gütschow, M.; Ragno, R.; Gomes, P. A. C.; Agrofoglio, L. A.; Muñoz-Torrero, D.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-4

Molecules 2019, 24, 130. Open Access Article

 

Barniol-Xicota, M.; Ruiz Santa Quiteria Saavedra, M.; Muñoz-Torrero, D. (eds.)

Present and Future of Medicinal Chemistry Research: A Young Researchers' Perspective (Special issue, 9 papers)

Molecules 2018, 23-24. Open Access Issue

 

Relat, J.; Come, J.; Perez, B.; Camps, P.; Muñoz-Torrero, D.; Badia, A.; Gimenez-Llort, L.; Clos, M. V.

Neuroprotective effects of the multitarget agent AVCRI104P3 in brain of middle-aged mice

Int. J. Mol. Sci. 2018, 19, 2615. Open Access Article

 

Mangoni, A. A.; Tuccinardi, T.; Collina, S.; Vanden Eynde, J. J.; Muñoz-Torrero, D.; Karaman, R.; Siciliano, C.; de Sousa, M. E.; Prokai-Tatrai, K.; Rautio, J.; Guillou, C.; Gütschow, M.; Galdiero, S.; Liu, H.; Agrofolio, L. A.; Sabatier, J.-M.; Hulme, C.; Kokotos, G.; You, Q.; Gomes, P. A. C.

Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-3

Molecules 2018, 23, 1596. Open Access Article

 

Alencar, N.; Sola, I.; Linares, M.; Juárez-Jiménez, J.; Pont, C.; Viayna, A.; Vílchez, D.; Sampedro, C.; Abad, P.; Pérez-Benavente, S.; Lameira, J.; Bautista, J. M.; Muñoz-Torrero, D.; Luque, F. J.

First homology model of Plasmodium falciparum glucose-6-phosphate dehydrogenase: Discovery of selective substrate analog-based inhibitors as novel antimalarial agents

Eur. J. Med. Chem. 2018, 146, 108-122.

 

Galdeano, C.; Coquelle, N.; Cieslikiewicz-Bouet, M.; Bartolini, M.; Pérez, B.; Clos, M.V.; Silman, I.; Jean, L.; Colletier, J.-P.; Renard, P.-Y.; Muñoz-Torrero, D.

Increasing polarity in tacrine and huprine derivatives: Potent anticholinesterase agents for the treatment of myasthenia gravis

Molecules 2018, 23, 634. Open Access Article

 

Ghashghaei, O.; Kielland, N.; Revés, M.; Taylor, M.C.; Kelly, J.M.; Di Pietro, O.; Muñoz-Torrero, D.; Pérez, B.; Lavilla, R.

Tetrasubstituted imidazolium salts as potent antiparasitic agents against African and American trypanosomiases

Molecules 2018, 23, 177. Open Access Article

 

Artigas, A.; Sola, I.; Taylor, M.C.; Clos, M.V.; Pérez, B.; Kelly, J.M.; Muñoz-Torrero, D.

Synthesis and biological evaluation of heteroarylnonanenitriles as potential antitrypanosomal agents: Serendipitous discovery of novel anticholinesterase hits

Lett. Org. Chem. 2018, 15, 455-461. (Special Issue dedicated to Prof. Miguel Yus, University of Alicante)

 

Relat, J.; Pérez, B.; Camps, P.; Muñoz-Torrero, D.; Badia, A.; Clos, M. V.

Huprine X attenuates the neurotoxicity induced by kainic acid, especially brain inflammation

Basic Clin. Pharmacol. Toxicol. 2018, 122, 94-103. Open Access Article

 

Muñoz-Torrero, D.; Mangoni, A. A.; Liu, H.; Hulme, C.; Rautio, J.; Karaman, R.; de Sousa, M. E.; Prokai-Tatrai, K.; Sabatier, J.-M.; Siciliano, C.; Luque, F. J.; Kokotos, G.; Ragno, R.; Collina, S.; Guillou, C.; Gütschow, M.; Agrofolio, L. A.

Editorial: Breakthroughs in Medicinal Chemistry: New Targets and Mechanisms, New Drugs, New Hopes-2

Molecules 2018, 23, 65. Open Access Article

 

Muñoz-Torrero, D.

Multitarget anti-Alzheimer hybrid compounds: Do they work in vivo?

in Design of Hybrid Molecules for Drug Development; Decker, M. (ed.); Elsevier, 2017, chapter 6, pp. 165-190.

 

Muñoz-Torrero, D.; Chibale, K. (eds.)

Emerging Drug Discovery Approaches against Infectious Diseases (Special issue, 27 papers)

Molecules 2017, 22-23. Open Access Issue

 

Muñoz-Torrero, D.; Lavilla, R.; Hulme, C. (eds.)

Multicomponent Reaction-Based Synthesis of Bioactive Molecules (Special issue, 7 papers)

Molecules 2017, 22-23. Open Access Issue

 

Muñoz-Torrero, D. (Ed.)

Proceedings of the 1st Molecules Medicinal Chemistry Symposium, Barcelona, Spain

MDPI Proceedings 2017, 1(6). Open Access Issue

</a>

Pérez-Areales, F. J.; Betari, N.; Viayna, A.; Pont, C.; Espargaró, A.; Bartolini, M.; De Simone, A.; Rinaldi Alvarenga, J. F.; Pérez, B.; Sabate, R.; Lamuela-Raventós, R. M.; Andrisano, V.; Luque, F. J.; Muñoz-Torrero, D.

Design, synthesis, and multitarget biological profiling of second generation anti-Alzheimer rhein-huprine hybrids

Fut. Med. Chem. 2017, 9, 965-981.

 

Di Pietro, O.; Juárez-Jiménez, J.; Muñoz-Torrero, D.; Laughton, C. A.; Luque, F. J.

Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: Conformational analysis and binding mode of multisite inhibitors

PLoS One 2017, 12, e0177683. Open Access Article

 

Muñoz-Torrero, D.; Mangoni, A. A.; Guillou, C.; Collina, S.; Vanden Eynde, J. J.; Rautio, J.; Keseru, G. M.; Hulme, C.; Chibale, K.; Luque, F. J.; Karaman, R.; Gütschow, M.; Liu, H.; Ragno, R.

Editorial: Breakthroughs in Medicinal Chemistry: New targets and mechanisms, new drugs, new hopes

Molecules 2017, 22, 743. Open Access Article

 

Espargaró, A.; Ginex, T.; Vadell, M. M.; Busquets, M. A.; Estelrich, J.; Muñoz-Torrero, D.; Luque, F. J.; Sabate, R.

Combined in vitro cell-based/in silico screening of naturally occurring flavonoids and phenolic compounds as potential anti-Alzheimer drugs

J. Nat. Prod. 2017, 80, 278-289.

 

Giménez-Llort, L.; Ratia, M.; Pérez, B.; Camps, P.; Muñoz-Torrero, D.; Badia, A.; Clos, M. V.

Behavioural effects of novel multitarget anticholinesterasic derivatives in Alzheimer’s disease

Behav. Pharmacol. 2017, 28, 124-131.

 

Decker, M.; Muñoz-Torrero, D. (eds.)

Molecules against Alzheimer (Special issue, 16 papers)

Molecules 2016, 20-21. Open Access Issue

 

Sola, I.; Artigas, A.; Taylor, M. C.; Pérez-Areales, F. J.; Viayna, E.; Clos, M. V.; Pérez, B.; Wright, C. W.; Kelly, J. M.; Muñoz-Torrero, D.

Synthesis and biological evaluation of N-cyanoalkyl-, N-aminoalkyl-, and N-guanidinoalkyl-substituted 4-aminoquinoline derivatives as potent, selective, brain permeable antitrypanosomal agents

Bioorg. Med. Chem. 2016, 24, 5162-5171. Open Access Article

 

Di Pietro, O.; Alencar, N.; Esteban, G.; Viayna, E.; Szalaj, N.; Vázquez, J.; Juárez-Jiménez, J.; Sola, I.; Pérez, B.; Solé, M.; Unzeta, M.; Muñoz-Torrero, D.; Luque, F. J. 

Design, synthesis and biological evaluation of N-methyl-N-[(1,2,3-triazol-4-yl)alkyl]propargylamines as novel monoamine oxidase B inhibitors

Bioorg. Med. Chem. 2016, 24, 4835-4854.

 

Kishore, K. G.; Ghashghaei, O.; Estarellas, C.; Mestre, M. M.; Monturiol, C.; Kielland, N.; Kelly, J. M.; Fortes Francisco, A.; Jayawardhana, S.; Muñoz-Torrero, D.; Pérez, B.; Luque, F. J.; Gámez-Montaño, R.; Lavilla, R.

Insertion of isocyanides into N-Si bonds: Multicomponent reactions with azines leading to potent antiparasitic compounds

Angew. Chem. Int. Ed. 2016, 55, 8994-8998.

 

Espargaró, A.; Medina, A.; Di Pietro, O.; Muñoz-Torrero, D.; Sabate, R.

Ultra rapid in vivo screening for anti-Alzheimer anti-amyloid drugs

Sci. Rep. 2016, 6, 23349. Open Access Article

 

Serrano, F. G.; Tapia-Rojas, C.; Carvajal, F. J.; Cisternas, P.; Viayna, E.; Sola, I.; Muñoz-Torrero, D.; Inestrosa, N. C.

Rhein-huprine derivatives reduce cognitive impairment, synaptic failure and amyloid pathology in AβPPswe/PS-1 mice of different ages

Curr. Alzheimer Res. 2016, 13, 1017-1029.

 

Navarro, S.; Carija, A.; Muñoz-Torrero, D.; Ventura, S.

A fast and specific method to screen for intracellular amyloid inhibitors using bacterial model systems

Eur. J. Med. Chem. 2016, 121, 785-792.

 

Sola, I.; Aso, E.; Frattini, D.; López-González, I.; Espargaró, A.; Sabaté, R.; Di Pietro, O.; Luque, F. J.; Clos, M. V.; Ferrer, I.; Muñoz-Torrero, D.

Novel levetiracetam derivatives that are effective against the Alzheimer-like phenotype in mice: synthesis, in vitro, ex vivo and in vivo efficacy studies

J. Med. Chem. 2015, 58, 6018-6032.

 

Di Pietro, O.; Vicente-García, E.; Taylor, M. C.; Berenguer, D.; Viayna, E.; Lanzoni, A.; Sola, I.; Sayago, H.; Riera, C.; Fisa, R.; Clos, M. V.; Pérez, B.; Kelly, J. M.; Lavilla, R.; Muñoz-Torrero, D.

Multicomponent reaction-based synthesis and biological evaluation of tricyclic heterofused quinolines with multi-trypanosomatid activity

Eur. J. Med. Chem. 2015, 105, 120-137. Open Access Article

 

Sola, I.; Castellà, S.; Viayna, E.; Galdeano, C.; Taylor, M. C.; Gbedema, S. Y.; Pérez, B.; Clos, M. V.; Jones, D. C.; Fairlamb, A. H.; Wright, C. W.; Kelly, J. M.; Muñoz-Torrero, D.

Synthesis, biological profiling and mechanistic studies of 4-aminoquinoline-based heterodimeric compounds with dual trypanocidal-antiplasmodial activity

Bioorg. Med. Chem. 2015, 23, 5156-5167 (Special issue New Developments in Antiinfectives Research).

 

Sola, I.; Viayna, E.; Gómez, T.; Galdeano, C.; Cassina, M.; Camps, P.; Romeo, M.; Diomede, L.; Salmona, M.; Franco, P.; Schaeffer, M.; Colantuono, D.; Robin, D.; Brunner, D.; Taub, N.; Hutter-Paier, B.; Muñoz-Torrero, D.

Multigram synthesis and in vivo efficacy studies of a novel multitarget anti-Alzheimer's compound

Molecules 2015, 20, 4492-4515. Open Access Article

 

Torrent, J.; Vilchez-Acosta, A.; Muñoz-Torrero, D.; Trovaslet, M.; Nachon, F.; Chatonnet, A.; Grznarova, K.; Acquatella-Tran Van Ba, I.; Le Goffic, R.; Herzog, L.; Béringue, V.; Rezaei, H.;

Interaction of prion protein with acetylcholinesterase: potential pathobiological implications in prion diseases

Acta Neuropathol. Commun. 2015, 3:18 Open Access Article

 

Giménez-Llort, L.; Ratia, M.; Pérez, B.; Camps, P.; Muñoz-Torrero, D.; Badia, A.; Clos, M.V.

AVCRI104P3, a novel multitarget compound with cognition-enhancing and anxyolitic actitivies: Studies in cognitively poor middle-aged mice

Behav. Brain Res. 2015, 286, 97-103.

 

Viayna, E.; Sola, I.; Bartolini, M.; De Simone, A.; Tapia-Rojas, C.; Serrano, F. G.; Sabaté, R.; Juárez-Jiménez, J.; Pérez, B.; Luque, F. J.; Andrisano, V.; Clos, M. V.; Inestrosa, N. C.; Muñoz-Torrero, D.

Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

J. Med. Chem. 2014, 57, 2549-2567.

 

Sola, I.; Artigas, A.; Taylor, M. C.; Gbedema, S. Y.; Pérez, B.; Clos, M. V.; Wright, C. W.; Kelly, J. M.; Muñoz-Torrero, D.

Synthesis and antiprotozoal activity of oligomethylene- and p-phenylene-bis(methylene)-linked bis(+)-huprines

Bioorg. Med. Chem. Lett. 2014, 24, 5435-5438.

 

Pérez-Areales, F. J.; Di Pietro. O.; Espargaró, A.; Vallverdú-Queralt, A.; Galdeano, C.; Ragusa, I. M.; Viayna, E.; Guillou, C.; Clos, M. V.; Pérez, B.; Sabaté, R.; Lamuela-Raventós, R. M.; Luque, F. J.; Muñoz-Torrero, D.

Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties

Bioorg. Med. Chem. 2014, 22, 5298-5307.

 

Di Pietro, O.; Pérez-Areales, F.J.; Juárez-Jiménez, J.; Espargaró, A.; Clos, M.V.; Pérez, B.; Lavilla, R.; Sabaté, R.; Luque, F.J.; Muñoz-Torrero, D.

Tetrahydrobenzo[h][1,6]naphthyridine-6-chlorotacrine hybrids as a new family of anti-Alzheimer agents targeting beta-amyloid, tau, and cholinesterase pathologies

Eur. J. Med. Chem. 2014, 84, 107-117.

 

Di Pietro, O.; Viayna, E.; Vicente-García, E.; Bartolini, M.; Ramón, R.; Juárez-Jiménez, J.; Clos, M.V.; Pérez, B.; Andrisano, V.; Luque, F.J.; Lavilla, R.; Muñoz-Torrero, D.

1,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studies

Eur. J. Med. Chem. 2014, 73, 141-152.

 

Pouplana, S.; Espargaró, A.; Galdeano, C.; Viayna, E.; Sola, I.; Ventura, S.; Muñoz-Torrero, D.; Sabate, R.

Thioflavin-S staining of bacterial inclusion bodies for the fast, simple, and inexpensive screening of amyloid aggregation inhibitors

Curr. Med. Chem. 2014, 21, 1152-1159.

 

Muñoz-Torrero, D.; Ferrer, I.; Sola, I.; Aso, E.

Multi-target drug compounds for the treatment of neurodegenerative disorders

Patent WO2014206877 A1 Date of priority: 2014

Main institution: Universitat de Barcelona / Institut d'Investigació Biomèdica de Bellvitge IDIBELL

 

Pera, M.; Camps, P.; Muñoz-Torrero, D.; Perez, B.; Badia, A.; Clos Guillen, M.V

Undifferentiated and differentiated PC12 cells protected by huprines against injury induced by hydrogen peroxide

PLoS One 2013, 8, e74344. Open Access Article

 

Viayna, E.; Sabate, R.; Muñoz-Torrero, D.

Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates

Curr. Top. Med. Chem. 2013, 13, 1820-1842.

 

Editor: Muñoz-Torrero, D.

Complexity against complexity: Multitarget drugs (Hot Topic issue, 12 chapters)

Curr. Med. Chem. 2013, 20, 1621-1799.

 

Viayna, E.; Sola, I.; Di Pietro, O.; Muñoz-Torrero, D.

Human disease and drug pharmacology, complex as real life

Curr. Med. Chem. 2013, 20, 1623-1634.

 

Ratia, M.; Giménez-Llort, L.; Camps, P.; Muñoz-Torrero, D.; Pérez, B.; Clos, M.V.; Badia, A.

Huprine X and huperzine A improve cognition and regulate some neurochemical processes related with Alzheimer's disease in triple transgenic mice (3xTg-AD)

Neurodegener. Dis. 2013, 11, 129-140.

 

Muñoz-Torrero, D.; Inestrosa, N.C.; Viayna, E.; Sola, I.; Vázquez, S.

Beta-amyloid-directed multitarget compounds for the treatment of Alzheimer’s disease

Patent PCT/EP2013/059683; US 9,238,626 B2. Date of priority: 2013

Main institution: Universitat de Barcelona / Pontificia Universidad Católica de Chile

 

Galdeano, C.; Viayna, E.; Sola, I.; Formosa, X.; Camps, P.; Badia, A.; Clos, M. V.; Relat, J.; Ratia, M.; Bartolini, M.; Mancini, F.; Andrisano, V.; Salmona, M.; Minguillón, C.; González-Muñoz, G. C.; Rodríguez-Franco, M. I.; Bidon-Chanal, A.; Luque, F. J.; Muñoz-Torrero, D.

Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer’s and prion diseases

J. Med. Chem. 2012, 55, 661-669.

 

Muñoz-Torrero, D.; Pera, M.; Relat, J.; Ratia, M.; Galdeano, C.; Viayna, E.; Sola, I.; Formosa, X.; Camps, P.; Badia, A.; Clos, M. V.

Expanding the multipotent profile of huprine-tacrine heterodimers as disease-modifying anti-Alzheimer agents

Neurodegener. Dis. 2012, 10, 96-99.

Dr. F. Javier Luque, Departament de Nutrició, Ciències de l’Alimentació i Gastronomia, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (Spain)

 

Dr. Mercè Pallàs / Dr. Christian Griñán-Ferré / Dr. Antoni Camins / Dr. Marta Barenys, Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (Spain)

 

Dr. Xavier Barril / Dr. Carles Galdeano / Dr. Jordi Juárez, Departament de Farmàcia i Tecnologia Farmacèutica i Fisicoquímica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (Spain)

 

Dr. Héctor García-Palmer / Dr. Isabel Puig-Borreil, Vall d’Hebron Institute of Oncology (VHIO), Barcelona (Spain)

 

Dr. Xavier Fernández-Busquets, Fundació Institut de Bioenginyeria de Catalunya (IBEC) / Fundació ISGlobal - Institut de Salut Global Barcelona

 

Dr. Raimon Sabaté, Departament de Farmàcia i Tecnologia Farmacèutica i Fisicoquímica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (Spain)

 

Dr. Belén Pérez, Departament de Farmacologia, de Terapèutica i de Toxicologia, Universitat Autònoma de Barcelona (Spain)

 

Dr. Manuela Bartolini, Department of Pharmacy and Biotechnology, University of Bologna (Italy)

 

Dr. Vincenza Andrisano / Dr. Angela De Simone, Department for Life Quality Studies, University of Bologna (Italy)

 

Dr. Nibaldo C. Inestrosa, Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Pontificia Universidad Católica de Chile (Chile)

 

Dr. Francisco Ciruela / Dr. Ester Aso, Institut de Neuropatologia, Servei d’Anatomia Patolo?gica, IDIBELL-Hospital Universitari de Bellvitge (Spain)

 

Dr. Rodolfo Lavilla, Departament de Farmacologia, Toxicologia i Química Terapèutica, Facultat de Farmàcia i Ciències de l’Alimentació, Universitat de Barcelona (Spain)

 

Dr. John M. Kelly, London School of Hygiene and Tropical Medicine (United Kingdom)

 

Dr. Colin W. Wrigth, Bradford School of Pharmacy (United Kingdom)

 

Dr. Bruce D. Hammock / Dr. Christophe Morisseau, Department of Entomology and Nematology, University of California Davis (USA)

 

Dr. Salvador Ventura, Institut de Biotecnologia i Biomedicina and Departament de Bioquimica i Biologia Molecular, Universitat Autònoma de Barcelona (Spain)

 

Dr. José Manuel Bautista, Departamento de Bioquímica y Biología Molecular IV and Instituto de Investigación Hospital 12 de Octubre, Universidad Complutense de Madrid (Spain)

 

Dr. Francesc Xavier Sureda, Departament de Ciències Mèdiques Bàsiques, Universitat Rovira i Virgili (Spain)

 

Dr. Pierre-Yves Renard / Dr. Ludovic Jean, COBRA – CNRS UMR 6014 & FR 3038, and Université de Rouen (France)

 

Dr. Jacques-Philippe Colletier, Institut de Biologie Structurale, Grenoble (France)

 

Dr. Diego Muñoz-Torrero                 Full Professor    dmunoztorrero@ub.edu

Dr. Ana Mallo                                   Postdoctoral researcher

Noemí Martínez                               PhD student

Aldrick B. Verano                             PhD student

Anna Sampietro                               PhD student

Javier Sánchez                                PhD student

Marc Granjé                                     Pregraduate student

Comparteix-ho: