Cytotoxic mechanisms of new antitumor nucleoside analogues, 3'-ethynylcytidine (ECyd) and 3'-ethynyluridine (EUrd).
The cytotoxic mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) were studied with mouse mammary tumor FM3A cells and human fibrosarcoma HT1080 cells. ECyd and EUrd are converted to ECyd 5'-triphosphate (ECTP) in the cells. ECTP has also outstanding stability in the cells; the half life of ECTP in FM3A cells was more than 3 days. The metabolisms and mechanisms of these analogues may play a key role in a potent antitumor activities against slow-growing solid tumors.
Kanda
H
H
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Takatori
S
S
Matsuda
A
A
Sasaki
T
T
Tanaka
M
M
Fukushima
M
M
Wataya
Y
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D001711:Biotransformation; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003562:Cytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D005354:Fibrosarcoma; D006801:Humans; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008956:Models, Chemical; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity
C103084:1-(3-C-ethynylribopentofuranosyl)cytosine; C103085:1-(3-C-ethynylribopentofuranosyl)uracil; D000964:Antimetabolites, Antineoplastic; D003562:Cytidine; D014529:Uridine