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.
Department of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak Technical University, Radlinského 9, SK-81237 Bratislava, Slovak Republic.
Zuzana
Z
Vantová
Helena
H
Paulíková
Danica
D
Sabolová
Mária
M
Kozurková
Mária
M
Suchánová
Ladislav
L
Janovec
Pavol
P
Kristian
Ján
J
Imrich
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