Person: Benhamú Salama, Bellinda
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First Name
Bellinda
Last Name
Benhamú Salama
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Química Orgánica
Area
Química Orgánica
Identifiers
5 results
Search Results
Now showing 1 - 5 of 5
Publication A new serotonin 5-HT 6 receptor antagonist with procognitive activity - Importance of a halogen bond interaction to stabilize the binding(Nature Publishing Group, 2017) González Vera, Juan Antonio; Medina Muñoz, Rocío Almudena; Martín Fontecha, María del Mar; Gonzalez Wong, Ángel; Fuente Mendizábal, Tania de la; Vázquez Villa, Henar; García Cárceles, Javier; Botta, Joaquín; McCormick, Peter J.; Benhamú Salama, Bellinda; Pardo Carrasco, Leonardo; López Rodríguez, María LuzSerotonin 5-HT 6 receptor has been proposed as a promising therapeutic target for cognition enhancement though the development of new antagonists is still needed to validate these molecules as a drug class for the treatment of Alzheimer's disease and other pathologies associated with memory deficiency. As part of our efforts to target the 5-HT 6 receptor, new benzimidazole-based compounds have been designed and synthesized. Site-directed mutagenesis and homology models show the importance of a halogen bond interaction between a chlorine atom of the new class of 5-HT 6 receptor antagonists identified herein and a backbone carbonyl group in transmembrane domain 4. In vitro pharmacological characterization of 5-HT 6 receptor antagonist 7 indicates high affinity and selectivity over a panel of receptors including 5-HT 2B subtype and hERG channel, which suggests no major cardiac issues. Compound 7 exhibited in vivo procognitive activity (1 mg/kg, ip) in the novel object recognition task as a model of memory deficit.Publication Discovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for “Diabesity”(ACS, 2022) Decara, Juan M.; Vázquez Villa, Henar; Brea, José; Alonso, Mónica; Srivastava, Raj Kamal; Orio Ortiz, Laura; Alen Fariñas, Francisco; Suárez, Juan; Baixeras, Elena; García Cárceles, Javier; Escobar Peña, Andrea; Lutz, Beat; Rodríguez, Ramón; Codesido, Eva; Garcia Ladona, F. Javier; Bennett, Teresa A.; Ballesteros, Juan A.; Cruces, Jacobo; Loza, María I.; Benhamú Salama, Bellinda; Rodríguez de Fonseca, Fernando; López Rodríguez, María L.Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small molecules acting as positive allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4- {[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)- piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-molecule PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes.Publication New Trends in Aging Drug Discovery(MDPI, 2022-08-15) Benhamú Salama, Bellinda; Martín Fontecha, María del Mar; Vázquez Villa, Henar; López Rodríguez, María Luz; Ortega Gutiérrez, SilviaAging is considered the main risk factor for many chronic diseases that frequently appear at advanced ages. However, the inevitability of this process is being questioned by recent research that suggests that senescent cells have specific features that differentiate them from younger cells and that removal of these cells ameliorates senescent phenotype and associated diseases. This opens the door to the design of tailored therapeutic interventions aimed at reducing and delaying the impact of senescence in life, that is, extending healthspan and treating aging as another chronic disease. Although these ideas are still far from reaching the bedside, it is conceivable that they will revolutionize the way we understand aging in the next decades. In this review, we analyze the main and well-validated cellular pathways and targets related to senescence as well as their implication in aging-associated diseases. In addition, the most relevant small molecules with senotherapeutic potential, with a special emphasis on their mechanism of action, ongoing clinical trials, and potential limitations, are discussed. Finally, a brief overview of alternative strategies that go beyond the small molecule field, together with our perspectives for the future of the field, is provided.Publication Operaciones básicas de laboratorio en el contexto de los objetivos de desarrollo sostenible (ODS)(2023-07-27) Ortega Gutiérrez, Silvia; Benhamú Salama, Bellinda; Canales Mayordomo, Mª Ángeles; Gámez Márquez, Francisco de Asís; Muñoz Oliva, Mª Riansares; Pérez Corona, Mª Teresa; Cilleros Prados, Olga; Sobrino Díaz, Mª Lourdes; Fernández Cabellos, Daniel; Sánchez Merino, AnabelEn este proyecto se pretende sensibilizar a los estudiantes en la importancia de los objetivos de desarrollo sostenible (ODS), fomentar su compromiso con los mismos y mostrar como la química puede contribuir de forma concreta y significativa a la consecución de los ODS.Publication 2-(Fluoromethoxy)-4′-(S-methanesulfonimidoyl)-1,1′-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson’s Disease(ACS, 2022-08-31) García Cárceles, Javier; Vázquez Villa, Henar; Brea, José; Ladron de Guevara-Miranda, David; Cincilla, Giovanni; Sánchez Martínez, Melchor; Sánchez Merino, Anabel; Algar Lizana, Sergio; Teresa de los Frailes, María; Roberts, Richard S.; Ballesteros, Juan A.; Rodríguez de Fonseca, Fernando; Benhamú Salama, Bellinda; Loza, María I.; López Rodríguez, María L.Tolerance development caused by dopamine replacement with L-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson’s disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4′- (S-methanesulfonimidoyl)-1,1′-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances L-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson’s disease.