In vitro screening of 1-aryl-6-hydroxy-1,2,3,4-tetrahydroisoquinolines: Structure related activity against pathogenic bacteria

Abstract

Objective: To evaluate the antibacterial activity of ten synthetic tetrahydroisoquinolines against eight bacterial strains. Methods: The ten tetrahydroisoquinolines synthesized via base-catalyzed Pictet–Spengler cyclization were screened against a total of eight bacterial strains comprising control and pathogenic strains by the disc diffusion and micro-dilution methods. The most active compound was then assessed for cytotoxicity on human lymphocytes. Results: Six of the tetrahydroisoquinolines showed broad spectrum bacteriostatic activity. The zones of inhibition produced ranged from 7 to 23 mm for 200 μg per disc. The presence of a lipophilic substituent at the para position of the pendant phenyl group conferred the highest antibacterial activity. Compound 2 [1-(3,4-chlorophenyl)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline] was the most active and produced zones ranging from 9 to 20 mm against all eight bacterial strains. Compound 2 also showed the lowest minimum inhibitory concentration of 100 μg/mL against Escherichia coli ATCC11775 and the lowest minimum bactericidal concentration of 800 μg/mL against pathogenic Salmonella typhimurium. Overall, compound 2 was the most active with bacteriostatic and bactericidal activity against three and four bacterial strains respectively. A 50% cytotoxic concentration of 98.2 μg/mL was recorded for compound 2 indicating a low risk of toxicity. Conclusions: The 1-aryl-1,2,3,4-tetrahydroisoquinolines display structure-related antibacterial activity and further chemical exploration of the tetrahydroisoquinoline scaffold may yield more potent non-toxic derivatives for development into new antibacterials.

Keywords

• Antibiotics
• Drug discovery
• Antibacterial agents
• Tetrahydroisoquinolines
• Cytotoxicity