A series of 6-(hydroxy1amino)purine and -1-deazapurine nucleosides were synthesized and tested for their antitumor and adenosine deaminase inhibitory activity. All the examined molecules displayed an in vitro activity comparable to that of the reference compounds 6-HydroxyLamino)-9-b-D-ribofuranosylpurine (HAPR) and ara-A, their ID50, ranging from 0.9 microM (16) to - 100 microM (12). The 6-hydroxylamino derivatives of l-deazapurine 9,12, and 17 and also the blocked compound 13 are inhibitors of ADA whereas the purine derivatives 4 and 6 and the nitro compounds 11 and 16 are resistant to the enzyme. 7-(Hydroxylamino)-3-(2-deoxy-b-D-erythro-pentofuranosyl)-3H-imidazo[4,5- b-pyridine (12), the less cytotoxic but the most active ADA inhibitor in the series (Ki = 2.7 x 10-7) greatly potentiates the antitumor activity of ara-A in vitro.

Purine and 1-deazapurine ribonucleosides and deoxyribonucleosides: synthesis and biological activity

CRISTALLI, Gloria;VITTORI, Sauro;GRIFANTINI, Mario;VOLPINI, Rosaria;LUPIDI, Giulio;
1991

Abstract

A series of 6-(hydroxy1amino)purine and -1-deazapurine nucleosides were synthesized and tested for their antitumor and adenosine deaminase inhibitory activity. All the examined molecules displayed an in vitro activity comparable to that of the reference compounds 6-HydroxyLamino)-9-b-D-ribofuranosylpurine (HAPR) and ara-A, their ID50, ranging from 0.9 microM (16) to - 100 microM (12). The 6-hydroxylamino derivatives of l-deazapurine 9,12, and 17 and also the blocked compound 13 are inhibitors of ADA whereas the purine derivatives 4 and 6 and the nitro compounds 11 and 16 are resistant to the enzyme. 7-(Hydroxylamino)-3-(2-deoxy-b-D-erythro-pentofuranosyl)-3H-imidazo[4,5- b-pyridine (12), the less cytotoxic but the most active ADA inhibitor in the series (Ki = 2.7 x 10-7) greatly potentiates the antitumor activity of ara-A in vitro.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11581/241441
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