5'-Esters of 2'-deoxyadenosine and 2-chloro-2'-deoxyadenosine with cell differentiation-provoking agents.

• Authors: Paweł Grieb , Tomasz Kryczka , Radosław Wójtowicz , Jerzy Kawiak , Zygmunt Kazimierczuk
• Languages of publication: EN

Abstracts

EN

Phenylacetic and retinoic acids are carboxyacidic cell differentiating agents displaying anticancer activities. We report on a new class of compounds including the 5'-esters of 2'-deoxyadenosine (dA) or 2-chloro-2'-deoxyadenosine (cladribine, 2CdA) and the aforementioned acids. The rationale behind the synthesis of these esters was that if they are hydrolyzed inside the lymphoid cells, either dA will be removed from the intracellular environment by deamination, or 2CdA will be phosphorylated and accumulated. In either case targetted delivery of the differentiating agent to the lymphoid cells may be envisaged. The said compounds were synthesized by the Mitsunobu procedure employing triphenylphosphine and azadicarboxylic acid esters, and their stability was tested against various esterases. Esters of dA and 2CdA with phenylacetic acids were found to be resistant to enzymatic hydrolysis, whereas those with retinoic acids were efficiently hydrolyzed by commercially available hepatic esterase as well as by esterases present in the blood plasma and in diluted human lymphocyte lysate. Susceptibility to enzymatic hydrolysis was found to be a prerequisite of cytotoxic and/or differentiating activity of these esters in leukemic cell lines.

Keywords

EN

cladribine; phenylacetate; all-trans-retinoic acid; 2'-deoxyadenosine; nucleoside esters; 13-cis-retinoic acid

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2002
• Volume: 49
• Issue: 1
• Pages: 129-137

Dates

published

2002

received

2001-09-10

revised

2002-01-20

accepted

2002-02-19

Contributors

author

Paweł Grieb

• Laboratory of Experimental Pharmacology, Polish Academy of Sciences Medical Research Center, Warszawa, Poland

author

Tomasz Kryczka

• Laboratory of Experimental Pharmacology, Polish Academy of Sciences Medical Research Center, Warszawa, Poland

author

Radosław Wójtowicz

• Department of Clinical Cytology, Postgraduate Medical Education Center, Warszawa, Poland

author

Jerzy Kawiak

• Department of Clinical Cytology, Postgraduate Medical Education Center, Warszawa, Poland

author

Zygmunt Kazimierczuk

• Institute of Chemistry, Agricultural University, Warszawa, Poland

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