Purine analogues as antiparasitic agents

Abstract

As parasites cannot synthesise purines de novo and must salvage them from their hosts, purine salvage pathways have long been considered an attractive chemotherapeutic target. Recently, the discovery of specific transition-state inhibitors, the interest in antiviral nucleoside analogues due to AIDS and their potential in lymphoproliferative diseases gave a new impulse to this research field. Among the patents disclosed recently, only iminoribitol derivatives have documented antiparasitic activities, especially against nucleoside N-hydrolases (NH), purine nucleoside phosphorylase (PNP) and also against 5′-deoxy-5′-methylthioadenosine phosphorylase (MTAP), an enzyme at the border of polyamine biosynthesis and purine salvage. Disclosed compounds with modifications of the pentose ring aimed to mimic ATP, are only expected to have an antiparasitic activity. The last group of patents consists of carboxamidines and inhibitors of nucleoside transporters with potential antiparasitic effect. Antiparasite chemotherapy should benefit from the ongoing research in this field, if these promising molecules are effectively tested on parasite models.

Keywords::

• antiparasitic chemotherapy
• immucillin
• MTAP
• nucleoside hydrolase
• purine analogue
• purine nucleoside phosphorylase (PNP)
• purine salvage