Konference: 2007 3. ročník Dny diagnostické, prediktivní a experimentální onkologie
Nádorová biologie/imunologie/genetika a buněčná terapie
Téma: 03. Mechanismy účinku protinádorových léčiv a léčebných postupů
Číslo abstraktu: 010
Autoři: MUDr. Petr Džubák; MUDr. David Vydra; K. Doležal; E. Hauserová; P. Tarkowski; K. Václavíková; prof. Ing. Miroslav Strnad, CSC.,DSc.; doc. MUDr. Marián Hajdúch, Ph.D.
The cytokinins are one of the major groups of phytohormones, which
control key processes during plant growth and development. They
were first identified as a factor that promotes cell division in
the presence of auxin and sustained growth in cultured plant cells.
Systematic screening and testing on various cancer cell lines of
the in vitro cytotoxicity of 6-benzyladenosine, substituted
differently on the benzyl ring have been done. The most promising
compound of this study, 6-(2-hydroxy-3-methoxybenzylamino)purine
riboside, has been tested for its antitumour activity against
cancer cell lines derived from various tumors. The IC50 data
obtained from a calcein AM viability/cytotoxicity or MTT assay
showed the interesting cytotoxic properties of this substance in
contrast to other very similar derivatives which displayed much
lower activity in this assay. Therefore, these results support the
potential use of this compound in cancer, especially in the
treatment of leukaemias. The 6-benzylaminopurine riboside,
6-(2-hydroxy-3-methoxybenzylamino)purine riboside, and both prodrug
forms reduced the frequency of S-phase cells of the cancer cell
line CEM in antiproliferation assays. Further observed cellular
effects included inhibition of DNA and RNA synthesis. The leading
compound 6-(2-hydroxy-3-methoxybenzylamino)purine riboside as well
as its mono-acetylated PD01 and tetra-acetylated PD02 pro-drug
forms, respectively, were tested for its bioavailability after the
oral administration to eight week old female Balb/c mice. We have
confirmed that -(2-hydroxy-3-methoxybenzylamino)purine riboside is
not bioavailable, but a acetylated pro-drugs exhibited high
bioavailability, the plasmatic concentrations of free
6-(2-hydroxy-3-methoxybenzylamino)purine reached therapeutic ranges
(9.3 ?M/5.7 ?M), 2 or 4 hours following the prodrug administration.
Anticancer activity of pro-drugs was also analyzed in vivo using
P388D1 and K562 leukemia models.
Supported by grants awarded by the Czech Ministry of Education
(MSM 6198959216 and LC07017).
Datum přednesení příspěvku: 28. 11. 2007