Anti-malarial activity of N6-modified purine analogues

Plasmodium falciparum causes one of the deadliest forms of malaria and resistance to the currently available drugs makes it imperative to develop new, safe and potent drugs. Parasites such as P. falciparum are unable to synthesise purines de novo and to this end often have multiple purine uptake and salvage systems. With this in mind, we have designed and synthesised libraries of purine analogues as potential anti-malarial agents. Herein, we report three compounds with promising activity against the highly chloroquine-resistant VS1 P. falciparum namely: N6-hydroxyadenine (1c), 2-amino-N6-aminoadenosine (2b) and 2-amino-N6-amino-N6-methyladenosine (4b).

Herein we report the synthesis, in vitro and in vivo biological evaluation for a series of purine analogues as anti-malarial agents. N6-hydroxyadenine (1c), 2-amino-N6-aminoadenosine (2b) and 2-amino-N6-amino-N6-methyladenosine (4b) displayed the most promising activity and were found to be non-toxic.Figure optionsDownload as PowerPoint slide