Table 2.

Biological activity of TryS inhibitors against the infective stage of different trypanosomatids (bloodstream T. brucei and intracellular amastigotes of T. cruzi and L. donovani) and mammalian (host) cells.

	Cytotoxicity (EC50 μM)a and selectivity index [SI]b
Compoundc	T. bruceid [SI vs. THP-1]	T. cruzid [SI vs. U-2 OS/THP-1 ]	L. donovanid [SI vs. THP-1]
1	>25	ND	>100
2	2.1 ± 0.2 [48]	ND	ND
3	>25	∼34 [2.7 / >2.7]	>100
4	0.34 ± 0.01 [29]	0.56 ± 0.01 [2.6 /∼18]	3.2 ± 0.6 [∼3]
5	8.9 ± 0.7 [11]	2.8 ± 0.1 [2.4 / >36]	>100
6	ND	0.37 ± 0.11 [1.3 / 9.5]	1.7 ± 0.2 [2]
7	0.55 ± 0.03 [182]	1.6 ± 0.1 [1.1 / >55.6]	>100
8	4.6 ± 0.5 [20]	ND	∼ 56 [∼1.4]
9	>25	ND	ND
10	ND	ND	4.5 ± 0.7 [1.6]
11	ND	ND	26.0 ± 8.1 [1.1]
12	5.9 ± 0.5 [14]	ND	ND
13	ND	ND	31 ± 5 [1.9]
14	5.2 ± 3.2 [11]	ND	ND
15	>25	ND	ND
16	>25	ND	ND
17	>25	ND	ND
18	>25	ND	ND
19	∼20 [>4]	ND	ND
20	>25	ND	ND
21	∼25 [>4]	ND	ND
22	ND	ND	>100
23	17.1 ± 4.4 [>6]	ND	ND
24	>25	ND	ND
25	>25	ND	ND
26	>25	ND	ND
27	>25	ND	ND
28	>25	ND	ND
29	∼25 [>4]	ND	ND
Nifurtimox	15.0 ± 2.5	ND	ND
Benznidazole	ND	2.5 ± 0.2 [>40]	ND
Amphotericin B	ND	ND	0.18 ± 0.02 [>22]

^aThe effect of the compounds in trypanosomatids viability is expressed as EC₅₀ (half-maximum effective concentration). The values correspond to the mean ± SD (n = 3). For some compounds the EC₅₀ reported corresponds to the closest concentration reducing cell viability to 45–55% and is indicated with the symbol “∼”.

^bThe selectivity index is calculated as the quotient CC₅₀ (half-maximum mammalian cytotoxic concentration)/EC₅₀ for the indicated host cell/pathogen pair.

^cCompounds 1–13 (grey background) and 14–29 correspond to hits from the in-house and ENAMINE library, respectively.

^dND: not determined.