Figure 2
α-PanAm inhibits growth of drug-sensitive and drug-resistant P. falciparum strains in a pantothenic acid-dependent manner. (A) Chemical synthesis route for α-PanAm. The 4 steps (a, b, c and d) of synthesis are described in details in Material and Methods. (a) di-tert-butyl dicarbonate, 1,4-dioxane, aq. NaOH, 5–25 °C. (b) phenethylamine, EDCI, pyridine, THF, 0 °C. (c) TFA, DCM, 25 °C. (d) methanol, 40 °C, 16 h. (B) growth curve of P. falciparum NF54, HB3 and W2 in human erythrocytes on complete RPMI medium lacking or supplemented with increasing concentrations of α-PanAm. (C) Growth of P. falciparum (NF54 strain) in human erythrocytes in complete RPMI medium (1.14 µM pantothenic acid) containing albumax supplemented with increasing concentrations of pantothenic acid (PA) and α-PanAm. Starting parasitemia was 1%. (D) Stage specificity of inhibition of P. falciparum by α−PanAm, P. falciparum culture was initiated at 1% starting parasitemia in human erythrocytes and α-PanAm applied at 0, 12 and 24 h. Parasite stages were monitored by light microscopy after Giemsa staining.
