The structure of anthracycline derivatives determines their subcellular
localization and cytotoxic activity
#MMPMID24900668
Shaul P
; Frenkel M
; Goldstein EB
; Mittelman L
; Grunwald A
; Ebenstein Y
; Tsarfaty I
; Fridman M
ACS Med Chem Lett
2013[Mar]; 4
(3
): 323-8
PMID24900668
show ga
The cytotoxic activities and subcellular localizations of clinically used and
synthetic analogues of the anthracycline family of chemotherapeutic agents were
studied. The structures of the anthracycline derivatives affected their
cytotoxicity and the time required for these compounds to exert cytotoxic effects
on tumor cells. Fluorescent DNA intercalator displacement experiments
demonstrated that there was no correlation between the DNA intercalation
properties and the cytotoxicity of the studied anthracycline derivatives.
Confocal microscopy experiments indicated that structural differences led to
differences in subcellular localization. All studied anthracycline derivatives
were observed in lysosomes, suggesting that this organelle, which is involved in
several processes leading to malignancy, may contain previously unidentified
molecular targets for these antitumor agents.
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