In vitro antileukemic activity of novel adenosine derivatives bearing boron cluster modification.
A series of adenosine derivatives bearing a boron cluster were synthesized and evaluated for their cytotoxicity against primary peripheral mononuclear cells from the blood of 17 patients with leukemias (16 CLL and 1 very rare PLL), as well as from 5 healthy donors used as a control. Among the tested agents, two, i.e., compounds 1 and 2, displayed high in vitro cytotoxicity and proapoptotic potential on leukemic cells, with only scarce activity being seen against control cells. Biological tests related to apoptosis revealed the activation of the main execution apoptotic enzyme, procaspase-3, in CLL and PLL cells exposed to compounds 1 and 2. Moreover, the above compounds indicated high activity in the proteolysis of the apoptotic markers PARP-1 and lamin B1, fragmentation of DNA, and the induction of some changes in the expression of the Mcl-1, protein apoptosis regulator in comparison with control cells.
Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, Poland.
Jolanta D
JD
Żołnierczyk
Screening Laboratory, Institute of Medical Biology Polish Academy of Sciences, Lodowa 106, 92-232 Łódź, Poland.
Agnieszka B
AB
Olejniczak
Department of Biophysics, Institute of Biochemistry and Biophysics Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
Adam
A
Mieczkowski
Department of Hematology, Medical University of Łódź, Ciołkowskiego 2, 93-510 Łódź, Poland.
Jerzy Z
JZ
Błoński
Department of Cytobiochemistry, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, Poland.
Zofia M
ZM
Kiliańska
Department of Hematology, Medical University of Łódź, Ciołkowskiego 2, 93-510 Łódź, Poland.
Tadeusz
T
Robak
Laboratory of Molecular Virology and Biological Chemistry, Institute of Medical Biology Polish Academy of Sciences, Lodowa 106, 92-232 Łódź, Poland. Electronic address: zlesnikowski@cbm.pan.pl.
Zbigniew J
ZJ
Leśnikowski
D000241:Adenosine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001895:Boron / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D054403:Leukemia, Prolymphocytic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000241:Adenosine; D001895:Boron
Adenosine; Anti-leukemia activity; Apoptotic potential; Boron clusters; Cladribine; Fludarabine