Please use this identifier to cite or link to this item:
Title: New trimethoprim-like molecules: bacteriological evaluation and insights into their action
Author: Jorba, Marta
Pedrola, Marina
Ghashghaei, Ouldouz
Herráez, Rocío
Campos Vicens, Lluís
Luque Garriga, F. Xavier
Lavilla Grífols, Rodolfo
Viñas, Miquel
Keywords: Antibiòtics
Resistència als medicaments
Drug resistance
Issue Date: 12-Jun-2021
Publisher: MDPI
Abstract: 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 difusion assays on Petri dish, 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 ß-naphthylamide (PAßN) 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.
Note: Reproducció del document publicat a:
It is part of: Antibiotics, 2021, vol. 10, num. 6, p. 709
Related resource:
ISSN: 2079-6382
Appears in Collections:Articles publicats en revistes (Institut de Química Teòrica i Computacional (IQTCUB))
Articles publicats en revistes (Institut de Biomedicina (IBUB))
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Files in This Item:
File Description SizeFormat 
712756.pdf1.99 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons