PMID- 20349025
OWN - NLM
STAT- MEDLINE
DCOM- 20100610
LR  - 20171116
IS  - 1734-154X (Electronic)
IS  - 0001-527X (Linking)
VI  - 57
IP  - 1
DP  - 2010
TI  - Synthesis and biological activity of raltitrexed-carrier conjugates.
PG  - 83-7
AB  - Drugs used in chemotherapy give undesirable side effects, e.g., cardiotoxicity, 
      leucopenia, hair loss and others. Covalent binding of a drug with a carrier may 
      change its biodistribution, elimination and/or rate of transformation in the 
      organism. The aim of this work was to synthesize conjugates of anticancer drug - 
      raltitrexed (RTX) with lysozyme, bovine serum albumin (BSA), and dextran T40 and 
      to investigate their cytotoxicity and influence on the cell cycle in comparison 
      with the free drug. Before conjugation RTX was transformed into anhydride by 
      treatment with dicyclohexylcarbodiimide in dimethylformamide. Activated RTX was 
      added into aqueous solution of carriers at different pH (from 8.5 to 10.5) for 3 
      to 15 min. The reaction was stopped by reducing the pH to 7.0. Maximum yield of 
      the reaction was obtained at pH 10 for BSA as well as for dextran. The highest 
      level of substitution was obtained after 5 min of the reaction. In in vitro 
      experiments on three cell lines: SW707, LoVo and A549, all conjugates tested had 
      up to a few hundred times higher IC(50) than the free drug. Interestingly, it was 
      noticed that the conjugates based on dextran and albumin were more cytotoxic than 
      the free drug in the highest concentrations tested (1000 and 10000 ng/ml). The 
      influence of RTX and the conjugates on SW707 cell cycle was studied. RTX blocked 
      the cell cycle mostly in the G(0)-G(1) and S phase and increased the percentage 
      of apoptotic cells. Cells in the G(2)-M phase were not observed. The conjugates 
      blocked the cell cycle in the S phase and decreased the percentage of cells in 
      the G(0)-G(1) phase.
FAU - Jagiello, Monika
AU  - Jagiello M
AD  - Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy 
      of Sciences, Wroclaw, Poland.
FAU - Kanska, Urszula
AU  - Kanska U
FAU - Nevozhay, Dmitry
AU  - Nevozhay D
FAU - Boratynski, Janusz
AU  - Boratynski J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100322
PL  - Switzerland
TA  - Acta Biochim Pol
JT  - Acta biochimica Polonica
JID - 14520300R
RN  - 0 (Dextrans)
RN  - 0 (Quinazolines)
RN  - 0 (Thiophenes)
RN  - 27432CM55Q (Serum Albumin, Bovine)
RN  - EC 3.2.1.17 (Muramidase)
RN  - FCB9EGG971 (raltitrexed)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cattle
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Dextrans/*chemistry
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Mice
MH  - Muramidase/*chemistry
MH  - Neoplasm Transplantation
MH  - Quinazolines/*chemical synthesis/*pharmacology
MH  - Serum Albumin, Bovine/*chemistry
MH  - Thiophenes/*chemical synthesis/*pharmacology
EDAT- 2010/03/30 06:00
MHDA- 2010/06/11 06:00
CRDT- 2010/03/30 06:00
PHST- 2009/10/15 00:00 [received]
PHST- 2010/03/18 00:00 [revised]
PHST- 2010/03/20 00:00 [accepted]
PHST- 2010/03/30 06:00 [entrez]
PHST- 2010/03/30 06:00 [pubmed]
PHST- 2010/06/11 06:00 [medline]
AID - 10570183 [pii]
PST - ppublish
SO  - Acta Biochim Pol. 2010;57(1):83-7. Epub 2010 Mar 22.