The research activity of the NeuroDrugs Group at the Medicinal Chemistry Institute is focused on the design, synthesis, biological study, and further optimization of structurally diverse chemical entities for treating neurological diseases. We are especially interested in developing innovative neurogenic and photoswitchable neurodrugs, in the fields of the Regenerative Medicine and the Photopharmacology, respectively.

Regenerative Medicine is one of the most innovative therapeutic approaches for the treatment of different pathologies. Undoubtedly, it will be a mainstay of the future medicine, although nowadays there are still several obstacles to overcome, such as the development of therapies for the nervous system. Efficient regeneration of damaged tissues by an accident (e.g., trauma, stroke), by neurodegenerative diseases (e.g., Alzheimer, Parkinson, amyotrophic lateral sclerosis) or psychiatric conditions (e.g., mood disorders, anxiety, major depression) would be a great advance to achieve the definitive cure for these diseases. Indeed, the discovery of the existence of neural stem-cells niches in the adult human brain opens the door to the development of small molecules as restorative therapies for such pathologies. Our group is interested in contributing to the Regenerative Medicine by the discovery of new drugs able to promote neuro-regeneration by endogenous stimulation of the brain neurogenesis.

Targets involved in neurogenesis are huge and most of them remain to be determined. For this reason, we have focused initially our projects and resources on several targets with different degree of knowledge about their involvement in neuronal plasticity. We have chosen receptors of melatonin, serotonin, cannabinoids, and nicotine, as well as the Wnt/beta-catenin and the nuclear erythroid 2-related factor-antioxidant response elements (Nrf2-ARE) pathways as potential neurogenic targets. All of these pharmacological receptors are involved in the pathology of neurodegenerative and mental diseases and some of them may exert neuroprotective actions through antioxidant, anti-inflammatory and anti-excitotoxicity properties.


Photopharmacology has grown impressively in the last decade and recent findings in areas as diverse as chemistry, biology and pharmacy continue to provide new evidence of their therapeutic potential. Photopharmacology is based in the use of drugs that can be selectively activated and deactivated with irradiation of light at different wavelengths. The use of light provides a fine adjustment in the control of the administration of these drugs, with high spatial and temporal resolution. Photo-activation/deactivation can be achieved inside the organism by activated fluorescent compounds, or from the outside using minimally invasive optical fibres for the delivery of photon excitation in specific tissues. Therefore, the photo-switchable drugs that can be activated and deactivated by their interaction with light may avoid systemic side effects, commonly associated to conventional drugs.

Our group is now involved in developing photoswitchable drugs acting on different types of ion channels, such as nicotinic acetylcholine receptors (nAChR) and voltage-gated potassium-selective (Kv) channels.


New drugs against COVID-19: Screening of the group's libraries on a detection platform against SARS-CoV-2 and subsequent optimization by computer-aided rational design.

Rational design, synthesis, pharmacological evaluation and further optimization of innovative drugs for neurological diseases. We use computer-aided rational design to guide the generation of new families of multifunctional drugs capable of acting on different pharmacological targets (melatonin, serotonin, nicotine, and cannabinoid receptors, BACE-1, GSK-3beta, Nrf2, etc.)

Creation and screening of an in-house chemical library composed of about 1000 products with privileged structures to act in the nervous system. As a result of ongoing work on neurodegenerative disease projects, the group has created a computerized collection of compounds with privileged structures to act in the nervous system and which has already produced very positive results. After a screening campaign in oxidative stress cell models, two families of multifunctional mitochondrial neuroprotective drugs have been developed, which were first patented and then published in renowned scientific journals.

Development of biological and pharmacological tools of special interest to our research lines, as in vitro / in silico methods to evaluate biological and drug-like properties (e.g., oral absorption and CNS penetration). Moreover, we develop fluorescent probes for labelling membrane receptors.

Cores, A.; Abril, S.; Michalska, P.; Duarte, P.; Olives, A. I.; Martín, M. A.; Villacampa, M.; León, R.; and Menéndez, J. C. Bisavenathramide analogues as Nrf2 inductors and neuroprotectors in “in vitro” models of oxidative stress and hyperphosphorylation. Antioxidants, 2021, aceptado JCR Impact Factor (2019): 5.014 (D1).

Rodríguez-Franco, M. I. entre otros autores, CSIC White Paper – Scientific Challenges 2050 Volume 5. Brain, Mind & Behavior. ISBN 978-84-00-10746-8 ( Published on April 30, 2021.

Codony, S.; Calvó-Tusell, C.; Valverde, E.; Osuna, S.; Morisseau, C.; Loza, M. I.; Brea, J.; Pérez, C.; Rodríguez-Franco, M. I.; Pizarro-Delgado, J.; Corpas, R.; Griñán-Ferré, C.; Pallàs, M.; Sanfeliu, C.; Vázquez-Carrera, M.; Hammock, B. D.; Feixas, F.; Vázquez, S. From the Design to the In Vivo Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis. J. Med. Chem. 2021, 64 (9), 5429–5446. JCR Impact Factor (2019): 6.205 (D1 – 3/61 – Medicinal Chemistry).

Duarte, P.; Cuadrado, A.; and León, R. Monoamine Oxidase Inhibitors: from classic to new clinical approaches. Handbook of Experimental Pharmacology, 2021, 264, 164-259. Capitulo de Libro.

Delogu, G. L.; Kumar, A.; Gatto, G.; Bustelo, F.; Saavedra, L. M.; Rodríguez-Franco, M. I.; Laguna, R.; Viña, D. Synthesis and in Vitro Study of Nitro- and Methoxy-2-Phenylbenzofurans as Human Monoamine Oxidase Inhibitors. Bioorg. Chem. 2021, 104616.

Rojas-Prats, E.; Martinez-Gonzalez, L.; Gonzalo-Consuegra, C.; Liachko, N. F.; Perez, C.; Ramírez, D.; Kraemer, B. C.; Martin-Requero, Á.; Perez, D. I.; Gil, C.; de Lago, E.; Martinez, A. Targeting Nuclear Protein TDP-43 by Cell Division Cycle Kinase 7 Inhibitors: A New Therapeutic Approach for Amyotrophic Lateral Sclerosis. Eur. J. Med. Chem. 2021, 210.

Codony, S.; Pujol, E.; Pizarro, J.; Feixas, F.; Valverde, E.; Loza, M. I.; Brea, J. M.; Saez, E.; Oyarzabal, J.; Pineda-Lucena, A.; Pérez, B.; Pérez, C.; Rodríguez-Franco, M. I.; Leiva, R.; Osuna, S.; Morisseau, C.; Hammock, B. D.; Vázquez-Carrera, M.; Vázquez, S. 2-Oxaadamant-1-Yl Ureas as Soluble Epoxide Hydrolase Inhibitors: In Vivo Evaluation in a Murine Model of Acute Pancreatitis. J. Med. Chem. 2020, 63 (17), 9237–9257. JCR Impact Factor (2019): 6.205 (D1 – 3/61 – Medicinal Chemistry).

Michalska, P.; Mayo, P.; Fernández-Mendívil, C.; Tenti, G.; Duarte, P.; Buendia, I.; Ramos, M. T.; López, M. G.; Menéndez, J. C.; León, R. Antioxidant, Anti-Inflammatory and Neuroprotective Profiles of Novel 1,4-Dihydropyridine Derivatives for the Treatment of Alzheimer’s Disease. Antioxidants 2020, 9 (8), 650. JCR Impact Factor (2019): 5.014 (D1).

Michalska, P.; Tenti, G.; Satriani, M.; Cores, A.; Ramos, M. T.; García, A. G.; Menéndez, J. C.; León, R. Aza‐CGP37157‐lipoic Hybrids Designed as Novel Nrf2‐inducers and Antioxidants Exert Neuroprotection against Oxidative Stress and Show Neuroinflammation Inhibitory Properties. Drug Dev. Res. 2020, 81 (3), 283–294. JCR Impact Factor (2019): 1.902 (Q3).

Lassagne, F.; Duguépéroux, C.; Roca, C.; Perez, C.; Martinez, A.; Baratte, B.; Robert, T.; Ruchaud, S.; Bach, S.; Erb, W.; Roisnel, T.; Mongin, F. From Simple Quinoxalines to Potent Oxazolo[5,4- f ]Quinoxaline Inhibitors of Glycogen-Synthase Kinase 3 (GSK3). Org. Biomol. Chem. 2020, 18 (1), 154–162.

Espadinha, M.; Viejo, L.; Lopes, R. M. R. M.; Herrera-Arozamena, C.; Molins, E.; dos Santos, D. J. V. A.; Gonçalves, L.; Rodríguez-Franco, M. I.; Ríos, C. de los; Santos, M. M. M. Identification of Tetracyclic Lactams as NMDA Receptor Antagonists with Potential Application in Neurological Disorders. Eur. J. Med. Chem. 2020, 194, 112242. JCR Impact Factor (2019): 5.572 (D1 – 5/61 – Medicinal Chemistry).

Michalska, P.; Buendia, I.; Duarte, P.; FernandezMendivil, C.; Negredo, P.; Cuadrado, A.; López, M. G.; Leon, R. Melatonin-Sulforaphane Hybrid ITH12674 Attenuates Glial Response in Vivo by Blocking LPS Binding to MD2 and Receptor Oligomerization. Pharmacol. Res. 2020, 152, 104597. JCR Impact Factor (2019): 5.893 (D1).

González-Naranjo, P.; Pérez, C.; Girón, R.; Sánchez-Robles, E. M.; Martín-Fontelles, M. I.; Carrillo-López, N.; Martín-Vírgala, J.; Naves, M.; Campillo, N. E.; Páez, J. A. New Cannabinoid Receptor Antagonists as Pharmacological Tool. Bioorg. Med. Chem. 2020, 28 (19), 115672. JCR Impact Factor (2019): 3.073 (Q2 – 26 – Medicinal Chemistry).

Campello, L.; Kutsyr, O.; Noailles, A.; Michalska, P.; Fernández-Sánchez, L.; Martínez-Gil, N.; Ortuño-Lizarán, I.; Sánchez-Sáez, X.; de Juan, E.; Lax, P.; León, R.; García, A. G.; Cuenca, N.; Maneu, V. New Nrf2-Inducer Compound ITH12674 Slows the Progression of Retinitis Pigmentosa in the Mouse Model Rd10. Cell. Physiol. Biochem. 2020, 54 (1), 142–159. JCR Impact Factor (2019): 5.500 (Q1).

Di Martino, R. M. C.; Pruccoli, L.; Bisi, A.; Gobbi, S.; Rampa, A.; Martinez, A.; Pérez, C.; Martinez-Gonzalez, L.; Paglione, M.; Di Schiavi, E.; Seghetti, F.; Tarozzi, A.; Belluti, F. Novel Curcumin-Diethyl Fumarate Hybrid as a Dualistic GSK-3β Inhibitor/Nrf2 Inducer for the Treatment of Parkinson’s Disease. ACS Chem. Neurosci. 2020, 11 (17), 2728–2740.

Cores, Á.; Piquero, M.; Villacampa, M.; León, R.; Menéndez, J. C. NRF2 Regulation Processes as a Source of Potential Drug Targets against Neurodegenerative Diseases. Biomolecules 2020, 10 (6), 904. JCR Impact Factor (2019): 4.082 (Q1).

Herrera-Arozamena, C.; Estrada-Valencia, M.; Martí-Marí, O.; Pérez, C.; de la Fuente Revenga, M.; Villalba-Galea, C. A.; Rodríguez-Franco, M. I. Optical Control of Muscular Nicotinic Channels with Azocuroniums, Photoswitchable Azobenzenes Bearing Two N-Methyl-N-Carbocyclic Quaternary Ammonium Groups. Eur. J. Med. Chem. 2020, 200, 112403. JCR Impact Factor (2019): 5.572 (D1 – 5/61 – Medicinal Chemistry).

Nuñez-Borque, E.; González-Naranjo, P.; Bartolomé, F.; Alquézar, C.; Reinares-Sebastián, A.; Pérez, C.; Ceballos, M. L.; Páez, J. A.; Campillo, N. E.; Martín-Requero, Á. Targeting Cannabinoid Receptor Activation and BACE-1 Activity Counteracts TgAPP Mice Memory Impairment and Alzheimer’s Disease Lymphoblast Alterations. Mol. Neurobiol. 2020, 57 (4), 1938–1951. JCR Impact Factor (2019): 4.50 (Q1 – 46 – Neurosciences).

Herrera-Arozamena, C.; Estrada-Valencia, M.; Pérez, C.; Lagartera, L.; Morales-García, J. A.; Pérez-Castillo, A.; Franco-Gonzalez, J. F.; Michalska, P.; Duarte, P.; León, R.; López, M. G.; Mills, A.; Gago, F.; García-Yagüe, Á. J.; Fernández-Ginés, R.; Cuadrado, A.; Rodríguez-Franco, M. I. Tuning Melatonin Receptor Subtype Selectivity in Oxadiazolone-Based Analogues: Discovery of QR2 Ligands and NRF2 Activators with Neurogenic Properties. Eur. J. Med. Chem. 2020, 190, 112090. JCR Impact Factor (2019): 5.572 (D1 – 5/61 – Medicinal Chemistry).

Michalska, P.; León, R. When It Comes to an End: Oxidative Stress Crosstalk with Protein Aggregation and Neuroinflammation Induce Neurodegeneration. Antioxidants 2020, 9 (8), 740. JCR Impact Factor (2019): 5.014 (D1).

Estrada Valencia, M.; Herrera-Arozamena, C.; Pérez, C.; Morales-García, J. A.; Pérez-Castillo, A.; Laurini, E.; Pricl, S.; Ramos., E.; Romero, A.; Viña, D.; Rodríguez-Franco, M. I. New flavonoid – N,N-dibenzyl(N-methyl)amine hybrids: Multi-target-directed agents for Alzheimer´s disease endowed with neurogenic properties. J. Enzyme Inhib. Med. Chem. 2019, 34, 712–727 (DOI: 10.1080/14756366.2019.1581184).

Figueiró-Silva, J.; Antequera, D.; Pascual, C.; de la Fuente Revenga, M.; Volt, H.; Acuña-Castroviejo, D.; Rodríguez-Franco, M. I.; Carro, E. The melatonin analog IQM316 may induce adult hippocampal neurogenesis and preserve recognition memories in mice. Cell Transplant. 2018, 27, 423-437 (DOI: 10.1177/0963689717721217).

Estrada Valencia, M.; Herrera-Arozamena, C.; de Andrés, L.; Pérez, C.; Morales-García, J. A.; Pérez-Castillo, A.; Ramos, E.; Romero, A.; Viña, D.; Yáñez, M.; Laurini, E.; Pricl, S.; Rodríguez-Franco, M. I. Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer’s disease. Eur. J. Med. Chem. 2018, 156, 534-553 (DOI: 10.1016/j.ejmech.20168.07.026).

Del Cerro, P.; Alquézar, C.; Bartolomé, F.; González-Naranjo, P.; Pérez, C.; Carro, E.; Páez, J. A.; Campillo, N. E.; Martín-Requero, A. Activation of the cannabinoid type 2 receptor by a novel indazole derivative normalizes the survival pattern of lymphoblasts from patients with late-onset Alzheimer’s disease. CNS Drugs 2018, 32 (6), 579-591 (DOI: 10.1007/s40263-018-0515-7).

Páez, J. A.; Campillo, N. E. Innovative therapeutic potential of cannabinoid receptors as targets in Alzheimer’s disease and less well-known diseases. Curr. Med. Chem. 2018, 25, 1-38 (DOI: 10.2174/0929867325666180226095132).

Roca, C.; Requena, C.; Sebastian-Perez, V.; Malhotra, S.; Radoux, C.; Pérez, C.; Martinez, A.; Páez, J. A.; Blundell, T. L.; Campillo, N. E. Identification of new allosteric sites and modulators of AChE through computational and experimental tools. J. Enzyme Inhib. Med. Chem. 2018, 33, 1034-1047 (DOI: 10.1080/14756366.2018.1476502).

Morales-García, J.A.; de la Fuente-Revenga, M.; Alonso-Gil, S.; Rodríguez-Franco, M. I.; Feilding, A.; Pérez-Castillo, A.; Riba, J. The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Sci. Rep. 2017, 7 (1): 5309 (DOI: 10.1038/s41598-017-05407-9). De acuerdo con la Editorial del Grupo Nature, este trabajo tiene una puntuación Altmetric (que calcula una puntuación basada en la atención on line que recibe un artículo) de 59 y se encuentra en el percentil 95 de los artículos publicados de edad similar en todas las revistas científicas (, datos a 20/02/2019).

Estrada, M.; Pérez, C.; Soriano, E.; Laurini, E.; Romano, M.; Pricl, S.; Morales-García, J. A.; Pérez-Castillo, A.; Rodríguez-Franco, M. I. New neurogenic lipoic-based hybrids as innovative Alzheimer’s drugs with sigma-1 agonism and beta-secretase inhibition. Future Med. Chem. 2016, 8 (11), 1191-1207 (DOI: 10.4155/fmc-2016-0036).

de la Fuente Revenga, M.; Herrera-Arozamena, C.; Fernández-Sáez, N.; Barco, G.; García-Orue, I.; Sugden, D.; Rivara, S.; Rodríguez-Franco, M. I. New coumarin-based fluorescent melatonin ligands. design, synthesis and pharmacological characterization. Eur. J. Med. Chem. 2015, 103, 370-373 (DOI: 10.1016/j.ejmech.2015.09.003).

de la Fuente Revenga, M.; Fernández-Sáez, N.; Herrera-Arozamena, C.; Morales-García, J. A.; Alonso-Gil, S.; Pérez-Castillo, A.; Caignard, D.-H.; Rivara, S.; Rodríguez-Franco, M. I. Novel N-acetyl bioisosteres of melatonin: Melatonergic receptor pharmacology, physicochemical studies and phenotypic assessment of their neurogenic potential. J. Med. Chem. 2015, 58 (12), 4998-5014 (DOI: 10.1021/acs.jmedchem.5b00245). Este trabajo original recibió el honor de ser Portada del Journal of Medicinal Chemistry (

de la Fuente Revenga, M.; Pérez, C.; Morales-García, J. A.; Alonso-Gil, S.; Pérez-Castillo, A.; Caignard, D.-H.; Yáñez, M.; Gamo, A. M.; Rodríguez-Franco, M. I. Neurogenic potential assessment and pharmacological characterization of 6-methoxy-1,2,3,4-tetrahydro-β-carboline (pinoline) and melatonin – pinoline hybrids. ACS Chem. Neurosci. 2015, 6, 800-810 (DOI: 10.1021/acschemneuro.5b00041). Este trabajo original recibió el honor de ser Portada del ACS Chemical Neuroscience (

Dra. María Isabel Rodríguez Franco (Investigadora Científica)

Dr. Juan Antonio Páez Prósper (Científico Titular)

Dra. Concepción Pérez Martín (Titulada Superior Especializada)

Dr. Pedro González Naranjo (Titulado Superior en Actividades Técnicas y Profesionales)

Dr. Rafael León Martínez (Científico Titular)

Alba Sanz Velasco (Contrato de Garantía Juvenil – MICINN)

Pablo Duarte Florez (Predoctoral contratado)

Enrique Crisman Vigil (Predoctoral contratado)

Paloma Mayo (Predoctoral contratado)

Laura Vozmediano (Estudiante TFM)

Alvaro Torcal (Estudiante TFM)

Clara Gómez Serrano (Estudiante TFM)

Website of the Neurodrugs  Group
Website of the Chemoinformatics group
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