Preparations of vitamin D analogs, spirostanols and furostanols from diosgenin and their cytotoxic activities.
Vitamin D analogs 12 and 13 having a spiro ring in the side chain, various spirostanols 18-21, 26, 27, 29 and 37, and furostanols 34-36 having SCN and SeCN groups at the 26 position were prepared from diosgenin 1 via (20S,22R,25R)-spirost-1alpha,2alpha-epoxy-4,6-dien-3-one 19 as a key intermediate. The cytotoxic activities of these derivatives as well as 1 on scarcely P-gp-expressed HCT 116 cells and P-gp-overexpressed Hep G2 cells were examined by MTT assay. Furostanols 34 (IC(50) value: 4.9+/-0.3 microM) and 36 (IC(50) value: 1.3+/-0.2 microM) exhibited marked cytotoxic effects on HCT 116 cells, and spirostanol 29 (IC(50) value: 2.4+/-0.8 microM) and furostanol 36 (IC(50) value: 2.8+/-0.4 microM) on Hep G2 cells. Furthermore, the effects of vitamin D analog 12, spirostanol 26 and furostanol 36 on apoptosis-signaling pathways were investigated. Compounds 12 and 26 overexpressed p53 and Bax mRNAs, while compound 36 overexpressed only Bax mRNA.
Quan
Hong-Ji
HJ
College of Pharmacy, Yanbian University, Yanji, Jilin 133000, China.
Koyanagi
Jyunichi
J
Komada
Fusao
F
Saito
Setsuo
S
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004144:Diosgenin / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D013150:Spirostans / Q000138:chemical synthesis* / Q000494:pharmacology; D013261:Sterols / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D000970:Antineoplastic Agents; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D013150:Spirostans; D013261:Sterols; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D014807:Vitamin D; C041827:furostanol I; D004144:Diosgenin