Reactions of 26-Iodopseudodiosgenin and 26-Iodopseudodiosgenone with Various Nucleophiles and Pharmacological Activities of the Products

摘要

26-Iodopseudodiosgenin (8) and 26-iodopseudodiosgenone (9) were reacted with various nucleophiles (KSCN, KOCN, NaCN, NaN3 and various amines) to give pseudodiosgenin derivatives (4, 12, 16?20, 26) and pseudodiosgenone derivatives (5, 13, 21?25, 27), respectively. The reactions of 8 and 9 with KOCN gave the elimination products (10) and (11), respectively. The reaction of 9 with NaCN gave 5α,26- (14) and 5β,26-dicyanocholestan-3-one (15). The reaction of 8 with NaN3 gave triazepine derivative (30), while that of 9 gave 26-azidopseudodiosgenone (31). Compound 31 was converted into triazepine derivative (32) by heating at 120 °C. The cytotoxicity of the pseudodiosgenins and pseudodiosgenones on P-gp-underexpressing HCT 116 cells and P-gp-overexpressing Hep G2 cells was examined by MTT assay. Pseudodiosgenins 2, 4, 12 and 30 showed strong cytotoxic activity (IC50 values: 2.6±0.3?6.7±1.4 μM), as did pseudodiosgenones 3, 5, 11, 13, 21?25 and 27 (IC50 values: 1.3±0.3?6.4±0.3 μM) toward HCT 116 cells. Pseudodiosgenins 12, 16 and 30 (IC50 values: 1.2±0.7?2.2±0.6 μM) and pseudodiosgenones 22, 23, 25 and 27 (IC50 values: 0.6±0.1?2.5±0.3 μM) were highly cytotoxic to Hep G2 cells. Compounds 3 and 27 showed efficient antibacterial activity (MIC: 15.6, 10.4 μg/ml) and (MIC: 7.8, 15.6 μg/ml) against Bacillus subtilis and Staphylococcus aureus, respectively.