Inpharma 1329 - 16 Mar 2002

Phosphatidylcholine inhibitor G25shows promising antimalarial

activityInhibitors of phosphatidylcholine synthesis may

represent a new class of potent antimalarials, reports amultinational group of researchers. They explain thatphosphatidylcholine synthesis is integral to the intra-erythrocytic survival and development of human malariaparasites and is absent in uninfected matureerythrocytes.

According to the researchers, their leadphosphatidylcholine synthesis inhibitor G25 waseffective against laboratory strains of Plasmodiumfalciparum with pre-existing resistance to chloroquine,quinine, mefloquine and pyrimethamine and 4 clinical P.falciparum isolates from Africa that had varying degreesof resistance to chloroquine, quinine and cycloguanilembonate.

In vivo activity against P. falciparum . . .Moreover, P. falciparum infection in Aotus monkeys

was cleared 4 days after treatment with G25 dosages aslow as 0.03 mg/kg administered twice daily for 8 days.The researchers comment that G25 was as effective asquinine and pyrimethamine/sulfadoxine [fansidar] inclearing P. falciparum infection in this primate model atdosages that were far below those required forconventional antimalarials.

. . . and P. vivaxIn addition, G25 was able to clear P. vivax and P.

cynomolgi infections in rhesus monkeys, whichsuggests that reticulocyte-restricted malaria parasitesare also highly sensitive to phosphatidylcholineinhibitors.

These findings indicate that G25 ‘fulfills essential invitro and in vivo criteria for the development of a newclass of antimalarials’, according to the researchers.Wengelnik K, et al. A class of potent antimalarials and their specific accumulationin infected erythrocytes. Science 295: 1311-1314, 15 Feb 2002 800901028

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Inpharma 16 Mar 2002 No. 13291173-8324/10/1329-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved