Optimizing the structure of (salicylideneamino)benzoic acids: Towards selective antifungal and anti-staphylococcal agents
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
33493669
DOI
10.1016/j.ejps.2021.105732
PII: S0928-0987(21)00034-8
Knihovny.cz E-resources
- Keywords
- Aminobenzoic acids, Schiff bases, anti-biofilm activity, antibacterial activity, antifungal activity, cytotoxicity,
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Antifungal Agents * pharmacology MeSH
- Arthrodermataceae MeSH
- Benzoates pharmacology MeSH
- Gram-Negative Bacteria MeSH
- Gram-Positive Bacteria MeSH
- Humans MeSH
- Methicillin-Resistant Staphylococcus aureus * MeSH
- Microbial Sensitivity Tests MeSH
- Molecular Structure MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- Antifungal Agents * MeSH
- Benzoates MeSH
An increasing resistance of human pathogenic bacteria and fungi has become a global health problem. Based on previous reports of 4-(salicylideneamino)benzoic acids, we designed, synthesised and evaluated their me-too analogues as potential antimicrobial agents. Forty imines derived from substituted salicylaldehydes and aminobenzoic acids, 4-aminobenzoic acid esters and 4-amino-N-phenylbenzamide were designed using molecular hybridization and prodrug strategies. The target compounds were synthesized with high yields and characterized by spectral methods. They were investigated against a panel of Gram-positive and Gram-negative bacteria, mycobacteria, yeasts and moulds. The most active imines were tested to determine their cytotoxicity and selectivity in HepG2 cells. Dihalogenosalicylaldehydes-based derivatives showed potent broad-spectrum antimicrobial properties, particularly against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (minimum inhibitory concentrations, MIC, from 7.81 µM) and Enterococcus faecalis (MIC of ≥15.62 µM), yeasts (MIC from 7.81 µM) and Trichophyton interdigitale mould (MIC of ≥3.90 µM). Methyl 4-[(2-hydroxy-3,5-diiodobenzylidene)amino]benzoate 4h exhibited excellent in vitro activity along with low toxicity to mammalian cells. This compound is selective for staphylococci, Candida spp. and Trichophyton interdigitale. In addition, this imine was evaluated as a potential inhibitor of Gram-positive biofilms. The successful approach used provided some promising derivatives with more advantageous properties than the parent 4-(salicylideneamino)benzoic acids.
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