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: N(6)-hydroxyadenine (1c), 2-amino-N(6)-aminoadenosine (2b) and 2-amino-N(6)-amino-N(6)-methyladenosine (4b).
Too
Kathleen
K
Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
Brown
Daniel M
DM
Bongard
Emily
E
Yardley
Vanessa
V
Vivas
Livia
L
Loakes
David
D
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D011687:Purines; C030985:purine