Retargeting azithromycin analogues to have dual-modality antimalarial activity

Table 2 Ring-stage survival assay percent survival values from drug treated artemisinin-resistant and artemisinin-sensitive parasites

Modification	Compound	Cam3.II^sensitive 72 hr growth IC₅₀ (μM, ±SEM)	Cam3.II^resistant 72 hr growth IC₅₀ (μM, ±SEM)	Concentration of drug = 5% growth of Cam3.II^sensitive (μM)	Growth Cam3.II^{DHA resistant(R539T)} (%)
	DHA	0.007 (0.002)	0.011 (0.001)	0.05	41
	Azithromycin	30 (5.5)	30 (0.005)	100	1
Naphthalene	3	0.035 (0.004)	0.04 (0.004)	0.4	8
2-Chlorophenyl	5	0.2 (0.02)	0.28 (0.005)	0.5	6
7-Chloroquinoline	56	0.004 (0.001)	0.009 (0.001)	0.055	7
Quinolone	71	0.07 (0.007)	0.15 (0.03)	0.6	6

The μM concentration of drug (DHA, azithromycin, GSK-3, GSK-5, GSK-56 and GSK-71) that resulted in a 5% survival value for artemisinin-sensitive Cam3.II^sensitive parasites was then used to treat artemisinin-resistant Cam3.II^{DHA resistant(R539T)} parasites, and the resulting % parasite survival value for the resistant parasites is displayed in the table. The IC₅₀ value of the drugs against Cam3.II^sensitive and Cam3.II^resistant strains is also shown to indicate their overall potency against artemisinin-sensitive and artemisinin-resistant parasites. Parasites were incubated for one cycle (72 hrs) after pulsed drug treatment and washing prior to measurement of parasitaemia by flow cytometry. Data represent the mean of 2 experiments

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