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Fig. 4. | BMC Biology

Fig. 4.

From: Retargeting azithromycin analogues to have dual-modality antimalarial activity

Fig. 4.

Growth inhibition profiles of azithromycin analogues and control drugs with short-term and in-cycle drug treatments. a Early ring-stage P. falciparum parasites (0–4 hrs post-invasion) were treated with doubling dilutions of azithromycin analogues/control drugs for 0–6 hrs and 0–12 hrs prior to washing the drug out of cultures allowing growth to continue until parasites were 44 hrs old. A 0–44 hr continuous drug control treatment was also included. a Growth inhibition profile of GSK-3 (naphthalene), GSK-5 (substituted phenyl), GSK-66 (chloroquinoline), GSK-71 (quinoline), dihydroartemisinin (DHA) and chloroquine with very early ring-stage treatment across 0–6 hrs and 0–12 hrs post-invasion compared to a full in-cycle treatment. There was no significant difference in drug efficacy between the treatment times of GSK-5 or GSK-71 (P > 0.01). GSK-66 showed a significant difference between 0-6 hr vs 0–12 hr treatments (P < 0.0079) and 0–6 hr vs 0–44 hr (P = 0.001), but there was no significant difference in drug efficacy between 0-12 hr vs 0–44 hr treatments (P = 0.96). GSK-3 and DHA showed no significant difference in efficacy between treatment times (P > 0.01), with the exception of 0–6 hr vs 0–44 hr (P = 0.005 and P = 0.01, respectively). In contrast, chloroquine demonstrated a significant difference in drug efficacy between all treatment times (0–6 hr vs 0–12 hr P < 0.0001; 0–6 hr vs 0–44 hr P < 0.0001; 0–12 hr vs 0–44 hr P < 0.0001). Parasitemia was measured via flow cytometry 44 hrs post-invasion. Data represents the means of 3 or more experiments expressed as a percentage of non-inhibitory control and error bars represent ± SEM. Dose response IC50s compared using extra sum of squares F-test. Repeat measure data is available in Additional file 15 Supporting Value Data. b Representative Giemsa-stained thin blood smears showing the growth phenotypes seen for non-inhibitory media controls, and treatment with 2× IC90 of azithromycin analogues GSK-3 (0.74 μM), GSK-5 (0.62 μM), GSK-66 (0.034 μM), GSK-71 (0.18 μM) and control drugs DHA (0.003 μM) and chloroquine (0.222 μM) (bottom panels) 0–6 hrs post treatment and 0–12 hrs post treatment

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