TABLE 1.

Antileishmanial activity^a and toxicity in THP-1^b cells of bis-pyridinium compounds

Compound	EC50 (μM) (SI)c				THP-1 EC50 (μM)
	Promastigotes		Amastigotes
	L. major	L. donovani	L. major	L. donovani
VGP-106	21.55 ± 3.72	0.36 ± 0.09	13.07 ± 6.30 (15.8)	0.86 ± 0.46 (240.2)	206.54 ± 9.89
VGP-114	0.47 ± 0.04	0.61 ± 0.09	0.10 ± 0.03 (1000.6)	0.85 ± 0.04 (117.7)	100.06 ± 8.57
VGP-118	29.15 ± 5.73	0.65 ± 0.19	6.21 ± 1.02 (2.4)	0.18 ± 0.03 (85.3)	15.35 ± 3.99
VGP-130	0.50 ± 0.07	0.73 ± 0.11	0.09 ± 0.02 (903.7)	2.02 ± 0.05 (40.3)	81.34 ± 10.65
VGP-138	0.74 ± 0.19	2.11 ± 0.48	0.30 ± 0.16 (586.8)	4.01 ± 0.43 (43.9)	176.05 ± 20.75
VGP-146	0.21 ± 0.06	0.33 ± 0.07	0.10 ± 0.04 (156.1)	0.42 ± 0.01 (37.2)	15.61 ± 3.26
VGP-150	0.36 ± 0.11	0.77 ± 0.04	0.09 ± 0.03 (267)	0.55 ± 0.16 (43.7)	24.03 ± 5.42
VGP-162	0.40 ± 0.08	0.35 ± 0.02	0.37 ± 0.03 (29.6)	1.00 ± 0.08 (11.0)	10.97 ± 2.41
VGP-174	1.70 ± 0.01	0.34 ± 0.03	0.41 ± 0.05 (6.1)	0.86 ± 0.03 (2.8)	2.47 ± 0.05
VGP-182	2.51 ± 0.01	0.92 ± 0.2	0.42 ± 0.12 (11.2)	0.52 ± 0.12 (9.1)	4.71 ± 0.23
AmB	0.32 ± 0.02	0.21 ± 0.01	0.24 ± 0.01 (59.7)	0.28 ± 0.13 (51.1)	14.32 ± 4.10
Miltefosine	16.65 ± 1.23	6.60 ± 1.57	10.61 ± 0.89 (2.5)	0.88 ± 0.14 (30.5)	26.86 ± 3.08

^aParasites were grown as described in Materials and Methods for 72 h at 28°C (promastigotes) or 37°C (intracellular amastigotes) in the presence of increasing concentrations of compounds. Data are means ± standard deviations of three independent determinations.

^bTHP-1 cells were grown as described in Materials and Methods for 72 h at 37°C, in the presence of increasing concentrations of compounds. Cell viability was determined using an MTT-based assay. Amphotericin B (AmB) and miltefosine were used as the standard antileishmanial agents. Data are means ± standard deviations from three independent experiments.

^cSelectivity indexes (SI) were calculated by dividing the EC₅₀ for THP-1 by that for intracellular amastigotes.