Leishmania amazonensis trypanothione reductase: Evaluation of the effect of glutathione analogs on parasite growth, infectivity and enzyme activity

Figures & data

Scheme 1 Synthesis of glutathione analogs. Synthesis of tripeptides ASC-I-74A, ASC-I-74B, ASC-I-75A, ASC-I-74B: (i) N-α-benzyloxycarbonyl-L-glutamic acid α-benzyl 1, N-hidroxysuccinimide, dry dioxane, DCC, 0°C, 12 h, 98%; (ii) R = L-Leu or L-Val, H₂O, Et₃N, ester 2, THF, rt, 12 h, 76%; (iii) N-α-benzyloxycarbonyl-L-glutamyl(α-benzyl)-L-Leu 3 or L-Val 3′, N-hidroxysuccinimide, dry dioxane, DCC, 0°C, 12 h, 96%; (iv) W = Gly or L-Ala, H₂O, Et₃N, ester 4 or 4′, THF, rt, 12 h, ASC-I-74A: 85%; ASC-I-74B: 81%; ASC-I-75A: 83%; ASC-I-75B: 76%.

Table I.  Effect of glutathione analogs on Leishmania amazonensis infective promastigotes. Parasites were incubated with/without the analogs and after 24 h the LDs₅₀ were calculated.

Compound	LD50 μg/mL	LD50 μM
ASC-I-74A	188,6 ± 5,0	348,6
ASC-I-74B	134,7 ± 4,8	242,7
ASC-I-75A	115,7 ± 3,8	219,5
ASC-I-75B	174,4 ± 2,9	322,3
ASC-I-9	>320	ND
ASC-I-99	>320	ND
ASC-II-9V	>320	ND
ASC-I-98V	>320	ND

Figure 1 Effect of glutathione analogs on the activity of TR of Leishmania amazonensis infective promastigotes. The enzyme activity was measured by NADPH consumption.

Figure 2 Effect of glutathione analogs on parasite x macrophage interaction, after 24 h of incubation.

Figure 3 Effect of glutathione analogs on parasite x macrophage interaction, after 48 h of incubation.