Clitocine, [6-amino-5-nitro-(beta-D-ribofuranosylamino)pyrimidine] a natural nucleoside isolated by the mushroom Clitocybe inversa, has shown strong insecticidal activity and potent cytostatic effects against several leukemia cell lines. It was found to be a substrate and inhibitor of adenosine kinase. The carbocyclic clitocine analogue 2 was also found to be readly phophorylated by adenosine kinase and significantly active both in vitro and in vivo against influenza A virus (Singapore). The observation that, from the structural point of view, clitocine shows a biogenetic relationship with adenosine, prompted us to prepare analogues of the anti-HIV agents 2'.3'-dideoxy-3'-oxoadenosine (isoddA) and 9-[phosphonomethoxy)ethyl]adenine (PMEA), in which the adenine moiety is replaced from 4,6-diamino-5-nitropyrimidine, the clitocine aglycon. Synthesis, antiviral activity and structure-activity relathionships of the title compounds will be reported.
Synthesis and anti-HIV activity of isonucleosides and acyclic nucleotides related to clitocine
FRANCHETTI, Palmarisa;CAPPELLACCI, Loredana;GRIFANTINI, Mario;
1994-01-01
Abstract
Clitocine, [6-amino-5-nitro-(beta-D-ribofuranosylamino)pyrimidine] a natural nucleoside isolated by the mushroom Clitocybe inversa, has shown strong insecticidal activity and potent cytostatic effects against several leukemia cell lines. It was found to be a substrate and inhibitor of adenosine kinase. The carbocyclic clitocine analogue 2 was also found to be readly phophorylated by adenosine kinase and significantly active both in vitro and in vivo against influenza A virus (Singapore). The observation that, from the structural point of view, clitocine shows a biogenetic relationship with adenosine, prompted us to prepare analogues of the anti-HIV agents 2'.3'-dideoxy-3'-oxoadenosine (isoddA) and 9-[phosphonomethoxy)ethyl]adenine (PMEA), in which the adenine moiety is replaced from 4,6-diamino-5-nitropyrimidine, the clitocine aglycon. Synthesis, antiviral activity and structure-activity relathionships of the title compounds will be reported.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
