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

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 mg 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 mg/mL against Escherichia coli ATCC11775 and the lowest minimum bactericidal concentration of 800 mg/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 mg/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.

Synthesis of novel tetrahydroisoquinolines and study of their anti-fungal and contraceptive activities / 第二军医大学学报

Objective: To synthesize novel tetrahydroisoquinolines with both anti-fungal and contraceptive activities, so as to provide precursor structures for contraceptives with anit-fungal activities. Methods: 3,4-dimethoxyphenylethylamine was taken as the template and the title compounds were synthesized through Pictet-Spengler reaction, neutralization reaction, substitution, hydrolysis, and acylation. The anti-fungal activity and sperm-killing activity of the target compounds were tested in vitro. Results: Fourteen title compounds were obtained and they were: 2-octyl-6, 7-dimethyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrochloride(1), 2-nonyl-6, 7-dimethyl-1,2, 3,4-tetrahydro-isoquinoline hydrochloride(2), 2-decyl-6, 7-dimethy-1, 2, 3, 4-tetrahydro-isoquinoline hydrochloride(3), 2-dodecyl-6, 7-dimethyl-1,2,3,4-tetrahydro-isoquinoline hydrochloride(4), 2-dodecyl 6, 7-diacetoxy-1, 2,3,4-tetrahydro-isoquinoline hydrochloride(5), 2-pentyl-6,7-diacetoxy-1,2,3,4-tetrahydro-isoquinoline hydrobromide(6), 2-hexyl-6, 7-diacetoxy-1,2,3,4-tetrahydro-isoquinoline hydrobromide(7), 2-heptyl-6, 7-diacetoxy-1,2,3,4-tetrahydro isoquinoline hydrobromide (8), 2-octyl-6, 7-dimethyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(9), 2-nonyl-6, 7-dimethyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(10), 2-decyl-6, 7-dimethy-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(11), 2-dodecyl-6, 7-dihydroxyl 1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(12), 2-tetradecyl-6, 7-dihydroxyl-1, 2, 3, 4-tetrahydro-isoquinoline hydrobromide(13), and 2-cetyl-6, 7-dihydroxyl-1,2,3,4-tetrahydro-isoquinoline hydrobromide(14). Compounds 5-14 were firstly reported. It was found that all the 14 compounds had anti-fungal activity and 6 compounds also showed sperm-killing activities, with compounds 11, 12 having the strongest activities. Conclusion: A group of novel compounds with both anti-fungal and contraceptive activities have been synthesized, which provide a precursor structure for developing new contraceptives with anti-fungal activities.

Synthesis of novel 1, 2, 3, 4-tetrahydroisoquinolines and study of their anti-fungal activities / 第二军医大学学报

Objective: To design and synthesize novel tetrahydroisoquinolines with anti-fungal activities. Methods: 3,4-dimethoxyphenylethylamine was taken as the template and the title compounds were synthesized through Pictet-Spengler reaction, neutralization reaction, substitution, hydrolysis, and acylation. Results: Twelve title compounds were obtained and all of them were firstly reported. Besides, all the target compounds had anti-fungal activities. The anti-fungal activities of compounds 6-8 and 10-12 were similar to or stronger than that of fluconazole's. Conclusion: Title compounds obtained in this study belong to a new type of anti-fungal agent, which deserves further study.