New Trimethoprim-Like Molecules: Bacteriological Evaluation and Insights into Their Action

Marta Jorba, Marina Pedrola, Ouldouz Ghashghaei, Rocío Herráez, Lluis Campos-Vicens, Franciso Javier Luque ,Rodolfo Lavilla, Miguel Viñas

This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported.

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

Sampietro, A.; Pérez-Areales, F. J.; Martínez, P.; Arce, E. M.; Galdeano, C.; Muñoz-Torrero, D. Pharmaceuticals 2022, 15, 545

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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

Codony, S.; Pont, C.; Griñán-Ferré, C.; Di Pede-Mattatelli, A.; Calvó-Tusell, C.; Feixas, F.; Osuna, S.; Jarné-Ferrer, J.; Naldi, M.; Bartolini,…

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Disease-modifying treatment with I 2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model: a comparative study with donepezil

Vasilopoulou F, Rodríguez-Arévalo S, Bagán A, Escolano C, Griñán-Ferré C, Pallàs M. Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in…

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Inhibition of Soluble Epoxide Hydrolase Ameliorates Phenotype and Cognitive Abilities in a Murine Model of Niemann Pick Type C Disease

Griñán-Ferré C, Companys-Alemany J, Jarné-Ferrer J, Codony S, González-Castillo C, Ortuño-Sahagún D, Vilageliu L, Grinberg D, Vázquez S, Pallàs M.…

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A Novel NMDA Receptor Antagonist Protects against Cognitive Decline Presented by Senescent Mice.

Companys-Alemany J, Turcu AL, Bellver-Sanchis A, Loza MI, Brea JM, Canudas AM, Leiva R, Vázquez S, Pallàs M, Griñán-Ferré C.Pharmaceutics. 2020. 12(3). pii: E284. doi: 10.3390/pharmaceutics12030284.

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