A New Guanidine-Core Small-Molecule Compound as a Potential Antimicrobial Agent against Resistant Bacterial Strains

Author:

Morata-Moreno Noelia1,Pérez-Tanoira Ramón23ORCID,del Campo-Balguerias Almudena45ORCID,Carrillo-Hermosilla Fernando6ORCID,Hernando-Gozalo Marcos27ORCID,Rescalvo-Casas Carlos23ORCID,Ocana Ana V.8,Segui Pedro1,Alonso-Moreno Carlos45ORCID,Pérez-Martínez Francisco C.89,Molina-Alarcón Milagros89ORCID

Affiliation:

1. Department of Otorrinolaringology, Complejo Hospitalario Universitario, 02006 Albacete, Spain

2. Departamento de Microbiología Clínica, Hospital Universitario Príncipe de Asturias, 28805 Madrid, Spain

3. Departamento de Biomedicina y Biotecnología, Facultad de Medicina, Universidad de Alcalá, 28805 Madrid, Spain

4. Unidad nanoDrug, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, 02008 Albacete, Spain

5. Departamento Química Inorgánica, Orgánica y Bioquímica, Facultad de Farmacia de Albacete-Centro de Innovación en Química Avanzada (ORFEO-CINQA), Universidad de Castilla-La Mancha, 02008 Albacete, Spain

6. Departamento de Química Inorgánica, Orgánica y Bioquímica-Centro de Innovación en Química Avanzada (ORFEO-CINQA), Universidad de Castilla-La Mancha, 13071 Ciudad Real, Spain

7. Departamento de Química Orgánica y Química Inorgánica, Facultad de Farmacia, Universidad de Alcalá, 28805 Madrid, Spain

8. Instituto de Investigación en Discapacidades Neurológicas (IDINE), University of Castilla-La Mancha, 02001 Albacete, Spain

9. Department of Nursing, University of Castilla-La Mancha, 02071 Albacete, Spain

Abstract

The guanidine core has been one of the most studied functional groups in medicinal chemistry, and guanylation reactions are powerful tools for synthesizing this kind of compound. In this study, a series of five guanidine-core small molecules were obtained through guanylation reactions. These compounds were then evaluated against three different strains of Escherichia coli, one collection strain from the American Type Culture Collection (ATCC) of E. coli ATCC 35218, and two clinical extended-spectrum beta-lactamase (ESBL)-producing E. coli isolates (ESBL1 and ESBL2). Moreover, three different strains of Pseudomonas aeruginosa were studied, one collection strain of P. aeruginosa ATCC 27853, and two clinical multidrug-resistant isolates (PA24 and PA35). Among Gram-positive strains, three different strains of Staphylococcus aureus, one collection strain of S. aureus ATCC 29213, and two clinical methicillin-resistant S. aureus (MRSA1 and MRSA2) were evaluated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) experiments were reported, and the drop plate (DP) method was used to determine the number of viable suspended bacteria in a known beaker volume. The results from this assessment suggest that guanidine-core small molecules hold promise as therapeutic alternatives for treating infections caused by clinical Gram-negative and Gram-positive bacteria, highlighting the need for further studies to explore their potential. The results from this assessment suggest that the chemical structure of CAPP4 might serve as the basis for designing more active guanidine-based antimicrobial compounds, highlighting the need for further studies to explore their potential.

Publisher

MDPI AG

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