Synthesis and antifungal activity of N-trialkylsilyl derivatives of nystatin

Abstract

Reactions of the polyene macrolide antibiotic nystatin with trialkylchlorosilanes led to the formation of N-alkylsilyl derivatives. The physicochemical and biological properties of the resulting nystatin derivatives were studied. Organic silicon derivatives of nystatin had high levels of antifungal activity against a wide set of test strains. Biological studies showed that the acute toxicity (LD 50 ) of the resulting nystatin derivatives were 2 -3 times lower than that of the initial antibiotic. 322 0091-150X/08/4206-0322

Silyl modification of biologically active compounds. 13. Synthesis, cytotoxicity and antibacterial action of N‐methyl‐N‐(2‐triorganylsiloxyethyl)‐1,2,3,4‐tetrahydro(iso)quinolinium iodides

“…The course of the reaction was followed using data provided by gas chromatography-mass spectrometry (GC-MS). 13 Compound 9d was obtained following the procedure described for 9a, from 0.89 g (5.00 mmol) N-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline (1) and 1 Compound 9e was obtained following the procedure described for 9a, from 0.88 g (4.95 mmol) N-(2-hydroxyethyl)-1,2,3,4-tetrahydroisoquinoline (1) and 1.28 g (7.43 mmol) dimethyloctylsilane, as a clear yellow oil. Once the dehydrocondensation reaction had reached completion, the reaction mixture was cooled to room temperature and the solid traces were filtered off.…”

“…If necessary (presence of unreacted alcohol detected by TLC), more hydrosilane was added. 13 The resulting crude residue was purified by column chromatography on silica gel eluted with chloroform-methanol (4:1) to give the desired diethylmethylsilyl ether as a clear light-yellow liquid.…”

“…[6][7][8][9][10] Silylation of biologically active compounds, possessing hydrophilic functional groups, is one of the most effective methods for increasing lipophilicity, ensuring drug permeability through lipophilic barriers inside living organisms; silylation therefore can positively influence biological activity appearance or enhancement. [13] A 2 0 -O-tert-butyldimethylsilyl group was found to be necessary for optimal antiproliferative activity of N 6 ,5 0 -bis-ureidoadenosine nucleosides. [13] A 2 0 -O-tert-butyldimethylsilyl group was found to be necessary for optimal antiproliferative activity of N 6 ,5 0 -bis-ureidoadenosine nucleosides.…”

“…GC-MS (m/z, %): 332 (M + À CH 3 I À CH 3 , 5), 146 (M + À CH 3 I À CH 2 OSi(CH 3 7-H) 13. 144-145 C. LC-MS (m/z, %): 363 (M + À I + 1, 100); 346 (M + À CH 3 I À 1, 5).…”

New biotesting method with the application of modern impedance technologies

“…Однако наи-более приемлемым и адекватным в настоящее время признано использование для этих целей тестовых биосистем. При этом в качестве последних могут быть применены как одноклеточные [1][2][3][4][5][6][7][8], так и более высокоорганизованные организмы (такие, например, как планктон, растения, рыбы, крысы и т.п.) [6][7][8][9][10][11][12][13][14], а также культуры клеток их тканей, крови и т.д.…”