Phenylalanine derivatives active against Toxoplasma gondii brain cysts in mice

The action of phenylalanine derivatives against a cyst forming strain of To xoplasma gondii was tested in vitro and in vivo in mice. These compounds we re Phe-Phe-OMe (dipeptide methyl ester) 1 and its cyclized product, 3,6-dib enzyl-2,5-dioxopiperazine 2, Boc-L-Phe 3, L-Phe-OMe 4, Boc-L-Phe-L-Phe-OMe 5. After a 48 hr incubation in vitro, the compounds 3 and 5 induced a highe r inhibition than the control molecule, pyrimethamine. In the in vivo studi es, the compound 3 induced a 77 % decrease in the number of cerebral cysts, comparable to pyrimethamine. Compounds 1, 5 and 4 induced a decrease of ab out 63 % in the cyst number. A size reduction and an alteration of the wall of treated cysts were often noted. In a histological study, a reduction in cyst size without either inflammation or intervention of the nevroglial ce lls was observed. The present study provides evidence on the efficacy of ph enylalanine derivatives and especially Boc-Phe 3, against T.gondii brain cy sts in mice.