Reactions of 26-iodopseudodiosgenin and 26-iodopseudodiosgenone with various nucleophiles and pharmacological activities of the products

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 5 alpha,26- (14) and 5 beta,26-dicyanocholestan-3-one (15). The reaction of 8 with NaN3 gave triazepine derivative (30), while that of 9 gave 26-azido-pseudodiosgenone (31). Compound 31 was converted into triazepine derivative (32) by heating at 120 degrees 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 mu m), as did pseudodiosgenones 3, 5, 11, 13, 21-25 and 27 (IC50 values: 1.3 +/- 0.3-6.4 +/- 0.3 mu m) toward HCT 116 cells. Pseudodiosgenins 12, 16 and 30 (IC50 values: 1.2 +/- 0.7-2.2 +/- 0.6 mu m) and pseudodiosgenones 22, 23, 25 and 27 (IC50 values: 0.6 +/- 0.1-2.5 +/- 0.3 mu m) were highly cytotoxic to Hep G2 cells. Compounds 3 and 27 showed efficient antibacterial activity (MIC: 15.6, 10.4, mu g/ml) and (MIC: 7.8, 15.6 mu g/ml) against Bacillus subtilis and Staphylococcus aureus, respectively.