Cytotoxic effects of novel amphiphilic dimers consisting of 5-fluorodeoxyuridine and arabinofuranosylcytosine in cross-resistant H9 human lymphoma cells.
Various amphiphilic heterodinucleoside phosphates have recently been synthesized in order to overcome drug resistance. These agents contain 5-fluorodeoxyuridine (5-FdUrd) and arabinofuranosylcytosine (Ara-C). We now investigated the action of two of these novel dimers (#2 and #10) in sensitive and 5-FdUrd/Ara-C cross-resistant H9 human lymphoma cells. The dimers were compared with 5-FdUrd and Ara-C for growth inhibition, apoptosis induction, and cell-cycle effects. No significant difference in the cytotoxicity of dimer #2 could be observed between sensitive and 5-FdUrd/Ara-C cross-resistant H9 cells (IC50 values of 220 nM and 200 nM, respectively), indicating that further studies with this compound are warranted.
Saiko
Philipp
P
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Horvath
Zsuzsanna
Z
Illmer
Christoph
C
Madlener
Sibylle
S
Bauer
Wolfgang
W
Hoechtl
Thomas
T
Erlach
Natascha
N
Grusch
Michael
M
Krupitza
Georg
G
Mader
Robert M
RM
Jaeger
Walter
W
Schott
Herbert
H
Agarwal
Ram P
RP
Fritzer-Szekeres
Monika
M
Szekeres
Thomas
T
D000970:Antineoplastic Agents / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003561:Cytarabine / Q000737:chemistry / Q000633:toxicity*; D019281:Dimerization; D005467:Floxuridine / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D008223:Lymphoma / Q000473:pathology*; D010766:Phosphorylation
D000970:Antineoplastic Agents; D005467:Floxuridine; D003561:Cytarabine