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.

Nandeshi: a powerful inhibitor of human acrosin activity / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the inhibitory effect of Nandeshi, an acrosin inhibitor, on human acrosin activity.</p><p><b>METHODS</b>We collected sperm samples from 10 healthy fertile men and cultured them with Nandeshi at 30 degrees C for 5 minutes at the concentrations of 0. 100, 0.120, 0.144, 0.173, 0.207, 0.249, 0.299, 0.358 and 0.430 mmol/L, with the controls treated with a well-known acrosin inhibitor N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK) at 150.0, 189.8, 213.6, 240.3, 270.3, 304.1 and 342.1 mmol/L. Then we determined the residual activity of human acrosin by improved Kennedy assay.</p><p><b>RESULTS</b>The residual activity of acrosin was negatively correlated with the Nandeshi concentration, and Nandeshi exhibited an inhibition rate about 800 times that of TLCK.</p><p><b>CONCLUSION</b>Nandeshi has a powerful inhibitory effect on human acrosin, and improved Kennedy assay is a simple, practical and highly sensitive technique for the detection of human acrosin activity.</p>

Synthesis and antifungal activity of 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols / 药学学报

<p><b>AIM</b>A series of triazole antifungals were synthesized to search for novel triazole antifungals with more potent activity, less toxicity and broader spectrum.</p><p><b>METHODS</b>Nineteen 1-(1,2,4-triazolyl-1H-1-yl)-2-(2,4-diflurophenyl)-3-(4-substituted benzyl-1-piperazinyl)-2-propanols were designed and synthesized, on basis of the three dimensional structure of P450 cytochrome 14 alpha-sterol demethylase (CYP51) and their antifungal activities were also evaluated.</p><p><b>RESULTS</b>All the title compounds were first reported. Results of preliminary biological tests showed that most of the title compounds exhibited high activity against the eight common pathogenic fungi and the activities against deep fungi were higher than that against shallow fungi.</p><p><b>CONCLUSION</b>Most of the title compounds showed higher antifungal activities than Fluconazole and Terbinafine. Compound VIII-1, 10, 12, 17 showed best antifungal activity with broad antifungal spectrum and were chosen for further development.</p>