Mc. Chung et al., SYNTHESIS AND IN-VITRO EVALUATION OF POTENTIAL ANTICHAGASIC DIPEPTIDEPRODRUGS OF PRIMAQUINE, Journal of pharmaceutical sciences, 86(10), 1997, pp. 1127-1131
American trypanosomiasis (Chagas' disease) is an endemic parasitic dis
ease afflicting more than 20 million people in Latin America. Currentl
y, therapy is unsatisfactory and only two drugs are available. Primaqu
ine, an antimalarial drug, has trypanocidal activity. Dipeptide deriva
tives of primaquine, Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ, were synt
hesized. The choice of the peptides was based on the primary specifici
ty of cruzipain, the major cysteine proteinase from T. cruzi. The prod
rugs obtained were tested on the LLC-MK2 cell culture infected with tr
ypomastigotes forms of T. cruzi Phe-Arg-PQ, Lys-Arg-PQ, and Phe-Ala-PQ
were active in all stages.