Promising activity of tetrahydroisoquinolines against multidrug-resistant clinical Salmonella isolates and cytotoxicity against monkey kidney cells

Abstract

The high burden of Salmonella infections has been aggravated by the emergence and spread of multidrug-resistant strains affecting almost all antibiotic classes recommended for treatment. Several tetrahydroisoquinolines, both natural and synthetic, are important pharmaceuticals for a wide range of pathologies. Medicinal chemistry exploration of the tetrahydroisoquinoline scaffold has yielded analogues with considerable antimicrobial activity against bacteria, viruses, and fungi, amongst other pharmacological properties. We report here on a series of seventeen tetrahydroisoquinoline analogues of Dioncophyllines that were synthesized and screened against multidrug-resistant strains of Salmonella using standard methods. The cytotoxicity of selected compounds was assessed. Two compounds, 3b and 3n, were found to have activity, presenting zones of inhibition ≥ 20 mm and the best minimum inhibitory concentration (MIC) of 16 µg/mL), comparable to current anti-Salmonella drugs. Furthermore, most MBC:MIC ratios were < 4 which may indicate bactericidal activity. However, toxicity against monkey kidney cells was shown to be highly dependant on the substituent group. Further medicinal chemistry exploration based on active structures may yield a highly active antibacterial lead.