Purine and 1-deazapurine ribonucleosides and deoxyribonucleosides: synthesis and biological activity.
A series of 6-(hydroxylamino)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-beta-D-ribofuranosylpurine (HAPR) and ara-A, their ID50 ranging from 0.9 microM to approximately 100 microM. The 6-hydroxylamino derivatives of 1-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-beta-D-erythro-pentofuranosyl)-3H-imi dazo[4,5- b]pyridine, 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.
Cristalli
G
G
Dipartimento di Scienze Chimiche e, Università di Camerino, Italy.
Vittori
S
S
Eleuteri
A
A
Grifantini
M
M
Volpini
R
R
Lupidi
G
G
Capolongo
L
L
Pesenti
E
E
D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D011687:Purines / Q000138:chemical synthesis* / Q000627:therapeutic use; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D058892:Adenosine Deaminase Inhibitors; D000970:Antineoplastic Agents; D003853:Deoxyribonucleosides; D011687:Purines; D012263:Ribonucleosides