TABLE 3.

Bioactivities of bis-acridine compounds against T. b. brucei

Compound	T. b. brucei		HL-60 cells		Selectivity		Bioactivity against T. brucei at compound concn of 1.56 μM (%)e	Toxicity for MRC-5 cells at compound concn of 3.13 μM (%)f
	EC50 (nM)a	MIC (nM)b	EC50 (nM)	MIC (nM)	EC50 ratioc	MIC ratiod
1	218.0	10,000	9,470	>10,000	43	>1	100	100
2	1.1	1,000	244	10,000	214	10	100	100
3	0.7	1,000	144	10,000	209	10	100	100
4	1.3	1,000	120	1,000	91	1
5	1.4	1,000	142	10,000	98	10
6	1.9	1,000	270	10,000	140	10
7	0.9	100	1,180	10,000	1,326	100
8	1.4	1,000	491	10,000	348	10
9	1.8	100	1,480	10,000	836	100	60	0
10	0.9	1,000	225	10,000	242	10
11	6.4	10,000	491	>10,000	77	>1
12	3.5	1,000	1,650	10,000	469	10	100	0
13	2.4	1,000	270	10,000	111	10
14	8.6	1,000	1,650	10,000	191	10	100	20
15	25.0	1,000	3,140	10,000	125	10	100	0
16	5.8	1,000	3,040	10,000	524	10
17	1.4	100	119	7,000	86	70
18	31.0	1,000	26,300	>10,000	859	>10
Melarsoprol	16.0	100	4,270	100,000	267	>1,000

^aCompound bioactivity was measured after a 48-h incubation and expressed as EC₅₀, i.e., the effective concentration of compound for reducing the culture density to 50% of that of DMSO-treated cultures.

^bCompound bioactivity was also expressed as the MIC, i.e., the compound concentration that was 100% lethal.

^cDefined as EC₅₀(HL-60 cells)/EC₅₀(T. b. brucei).

^dDefined as MIC(HL-60 cells)/MIC(T. b. brucei). Each compound was tested in three separate experiments, and the standard deviations never exceeded 20% of the means.

^eData are from reference 17.

^fData are from reference 17. MRC-5 is a human diploid embryonic lung cell line.