Table 4.

In vivo antimalarial activity of selected new tetracyclines after intraperitoneal administration^a

Compound	IC50c (nM)	Dose (mg/kg)	Avg parasitemia score on dayb:
			7	8	10
PBS (control)			3	4	4*
Doxycycline	321	10	1.4	1.6	4
		50	0	0 (day 9)	0.6 (day 11)
Minocycline	102	20	0.2	1	1.6 (day 9)
MAL0919	22	10	0	0.2	1.2
MAL1570	53	10	0.4	0.8	4
MAL5001	28	10	0	0	0
MAL5002	18	10	0	0	0.2
MAL5003	34	10	0.6	1.4	4
MAL5004	46	10	0.2	0.2	1.6
MAL5008	25	10	0	0	0
MAL5011	44	10	0	0	0.4
MAL5012	37	10	0.2	1.6	4
MAL5021	19	10	0	0	0
MAL5022	21	10	0	0	0
MAL5028	27	10	0	0	0.2
MAL5061	47	10	0.4	0.6	4
MAL5064	43	10	0.6	0.8	4
MAL5086	26	10	0	0	0.6
MAL5113	22	10	0	0	0.2
MAL5155	52	50	0	0	0 (day 9)
MAL5166	21	20	0	0	0 (day 9)

^aSelected tetracyclines were tested in a P. berghei-based model of rodent malaria. Compounds were given by intraperitoneal administration once a day for 4 days at 10 mg/kg.

^bPercent parasitemia was scored on days 7, 8, and 10. Score 0, no parasites detected; 1, less than 1% parasitemia; 2, between 1 and 10% parasitemia; 3, greater than 10%; and 4, >50% parasitemia, at which point the animal was euthanized. Data are presented as the average score on a particular day for 5 animals. In some instances, parasitemia was evaluated on day 9 or 11 instead of day 10. The asterisk indicates that all control animals were euthanized on day 8.

^cIC₅₀ data are in vitro activity against P. falciparum as shown in Table 1.