. Author manuscript; available in PMC: 2010 Jul 9.

Published in final edited form as: J Med Chem. 2009 Jul 9;52(13):4038–4053. doi: 10.1021/jm900356n

Table 2.

Antigiardial Potency and Toxicity of New 5-NI Alkanes


					Activity against G. lamblia^a
entry	name	X	Y	R	EC₅₀ (nM)	pEC₅₀ (Mean ± SE)	toxicity in HeLa cells,^b pIC₅₀ (mean ± SE)	selectivity ratio,^c IC₅₀/EC₅₀
1	3	Br	Br	Me	65	7.19 ± 0.15	4.95 ± 0.06	174
2	33	Br	Br	Br	347	6.46 ± 0.15	5.10 ± 0.15	23
3	34	OH	OH	Me	832	6.08 ± 0.15	<4.00	> 120
4	35	OH	OH	Br	447	6.35 ± 0.19	4.04 ± 0.04	208
5	36	OAc	OAc	Me	316	6.50 ± 0.19	<4.00	> 319
6	37	OAc	OAc	Br	224	6.65 ± 0.16	4.01 ± 0.01	436
7	40	H	H	H	209	6.68 ± 0.18	<4.00	> 474
8	41	H	H	Me	282	6.55 ± 0.25	<4.00	> 357
9	42	H	H	Br	1148	5.94 ± 0.33	4.01 ± 0.01	85
10	Mz				2630	5.58 ± 0.09	2.22 ± 0.08	2291

Activity against G. lamblia was determined as EC₅₀, the compound concentration that inhibited growth of G. lamblia by 50% over the assay period, and is expressed as negative log₁₀ value of the EC₅₀ (pEC₅₀). Higher pEC₅₀ values reflect greater potency. Data are mean ± SE of the average pEC₅₀ of four different G. lamblia isolates (WB/C6, GS/M, 106, and 713). The average pEC₅₀ for each individual isolate is based on the results of three to four separate experiments. Mean EC₅₀ was calculated from the mean combined pEC₅₀ for all four isolates.

Toxicity against HeLa cells was determined as IC₅₀, the compound concentration that killed 50% of HeLa cells in the cytotoxicity assays, and is expressed as negative log₁₀ value of the IC₅₀ (pIC₅₀), with higher values reflecting greater toxicity. Data are the mean ± SE of the results of three separate experiments.

Selectivity ratio, the ratio of IC₅₀ to EC₅₀, reflects the relative selectivity of compound potency against Giardia compared to toxicity in HeLa cells, with higher ratios indicating greater selectivity for the parasite.