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Fig. 3. | BMC Biology

Fig. 3.

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

Fig. 3.

Azithromycin has broad activity against blood-stage parasites. a Early ring-stage P. falciparum parasites (0–4 hrs post-invasion) were treated with doubling dilutions of azithromycin and inhibition of growth measured for in-cycle (44 hr, IC50, 11 μM), 1-cycle (72 hr, IC50, 14 μM) and 2-cycle (delayed death, 120 hr, IC50, 0.07 μM) assays (44 hr vs 72 hr, P=NS; 120 hr vs 44 hr P < 0.0001; 120 hr vs 72 hr P < 0.0001). b Schematic of drug washout treatment scheme to assess azithromycin’s quick-killing stage of activity. Early ring-stage parasites (0–4 hrs post-invasion) were aliquoted to a 96-well plate and doubling dilutions of azithromycin added between 0-12 hrs, 12–24 hrs, 24–36 hrs and 36–44 hrs post invasion prior to drug removal by washing with fresh media. c Growth inhibition of azithromycin across 0–12 hrs, 12–24 hrs, 24–36 hrs and 36–44 hrs post invasion prior to drug removal by washing with fresh media. There was no significance between treatment times for 0–12 hrs, 12–24 hrs, 24–36 hrs, but there was for 0–12 hrs vs 36–44 hrs (P = 0.005), 12–24 hrs vs 36–44 hrs (P = 0.01) and 24–36 hrs vs 36–44 hrs (P = 0.01). d Growth inhibition of azithromycin with very early ring-stage treatment across 0–6 hrs and 0–12 hrs post-invasion compared to a full in-cycle (0–44 hr) treatment. Treatments showed significant difference (P < 0.0001) with the exception of 0–12 hrs vs 0–44 hrs (P = 0.19). For all growth curves, parasitemia was measured at 44 hrs post invasion at schizont stage via flow cytometry. 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. e Representative Giemsa-stained thin blood smears showing the growth phenotypes seen for non-inhibitory media controls (top panels) and in the presence of 2× IC90 concentration of azithromycin (bottom panels) across different stages of intraerythrocytic blood-stage development (0–6 hrs, 0–12 hrs, 12–24 hrs, 24–36 hrs and 36–44 hrs)

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