Abstract
Cytokins, N6-subsitued adenine derivatives play an important role in many different processes in plant development (
Mok et al,
), including the cell growth and division control, the vegetable cell differentiation with auxin and the storage of various metabolites as alkaloids (Annu Rev Plant. Physiol Plant Mol Biol
2001
, 52
:89
–118Yahia et al,
). Furthermore, several studies suggest that cytokinins and their purin derivated are able to control mammalian cell apoptosis and differentiation of human leukemic cells (HL-60 myeloblastic cell line) into mature granulocytes (Plant Science
1998
, 133
:9
–15Ishii et al,
). All these compounds exert their biological activity via Cyclin-Dependant Kinase (CDK) inhibition and particulary CDK1 and CDK2. The aim of our study was the synthesis of new 7-azaindole derivates as cytokinin analogues and the evaluation of their biological effects on HL-60 cells.Cell Growth Differ
2002
, 13
: 19
–26Eight analogues of 7-azaindole were prepared by the condension of (N-methyl-)4-chloropyrrolo[2,3-b]pyridine with corresponding amines using palladium-catalyzed reaction (
Hartwig et al,
). The four derivates from 1H-pyrrolo[2,3-b]pyridine were 4-phenylamino-7-azaindole, 4-benzylamino-7-azaindole, 4-phenethylamino-7-azaindole and 4-phenylpiperazylamino-7-azaindole. The four derivates from 1-methyl-pyrrolo[2,3-b]pyridine were 4-phenylamino-N-methyl-7-azaindole, 4-benzylamino-N-methyl-7-azaindole, 4-phenetylamino-N-methyl-7-azaindole and 4-phenylpiperazylamino-N-methyl-7-azaindole. HL-60 cells were exposed to three concentrations of these compounds (10–100–500 μM) during 72h at 37°C. The number of viable cells was determined by Trypan blue exclusion, and the cell cycle was assessed by propidium iodide staining followed by flow cytometric analysis. All these compounds decreased the number of viable cells. The compounds of the NH serie were more active than their methyl-analogues, especially 4-phenylamino-N-methyl-7-azaindole and 4-phenethylamino-7-azaindole which presented an estimated IC50 of 2 μM. Moreover, when used at 10 μM, 4-phenylamino-N-methyl-7-azaindole induced apoptosis whereas 4-phenethylamino-7-azaindole promoted inhibition of the cell cycle without pro-apoptotic effect.Angew Chem IN Ed
1998
, 37
: 2046
–2067These results suggest that cytokinin analogues derived from 1H-pyrrolo[2,3-b]pyridine may present interesting therapeutic potential as cytostatic agents. Further studies will clarify their biological effects on leukemic cells.
Disclosure: No relevant conflicts of interest to declare.
Author notes
*
Corresponding author
2006, The American Society of Hematology
2006
This feature is available to Subscribers Only
Sign In or Create an Account Close Modal