Cytotoxic activity of acridin-3,6-diyl dithiourea hydrochlorides in human leukemia line HL-60 and resistant subline HL-60/ADR.
A series of acridin-3,6-diyl-dithiourea hydrochloride derivatives (alkyl-AcrDTU) was prepared and tested against sensitive and drug resistant leukemia cell lines for their cytotoxic/cytostatic activity. The products (ethyl-, n-propyl-, n-butyl-, n-pentyl-AcrDTU) showed high DNA binding affinity via intercalation (K=7.6-2.9 x 10(5) M(-1)). All derivatives inhibited proliferation of HL-60 cells and its resistant subline HL-60/ADR, unexpectedly the resistant subline was more sensitive than the parental one (IC(50)=3.5 microM, 48-treatment of HL-60/ADR with pentyl-AcrDTU). Cytotoxicity of tested compounds was associated with their DNA-binding properties and the level of intracellular thiols has been changed in the presence of AcrDTU.
Vantová
Zuzana
Z
Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak Technical University, Radlinského 9, SK-81237 Bratislava, Slovak Republic.
Paulíková
Helena
H
Sabolová
Danica
D
Kozurková
Mária
M
Suchánová
Mária
M
Janovec
Ladislav
L
Kristian
Pavol
P
Imrich
Ján
J
D000166:Acridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D017186:Titrimetry; D044366:Transition Temperature
D000166:Acridines; D000970:Antineoplastic Agents; D004247:DNA; D013890:Thiourea