Figure 3

Figure 3

Berbamine analogs confer protection from aminoglycosides. (A,B) Dose-response curves for berbamine analog polymers and berbamine (parent compound) against 200 μM neomycin and 100 μM gentamicin. (C,D) Dose-response curves for the remainder of the berbamine analog polymers, and the berbamine analog monomers (BA-13 to BA-16) against 200 μM neomycin and 100 μM gentamicin. Zebrafish were pretreated for 1 h with each berbamine analog at variable doses followed by co-treatment with analog and aminoglycoside. Data are normalized to controls. Twelve analogs protected hair cells from neomycin damage, while 11 protected from gentamicin. Ten of the berbamine analogs were protective against both neomycin and gentamicin in a dose-dependent manner. Hair cells were assessed via DASPEI. Data are presented normalized to vehicle controls. Data were analyzed by one-way ANOVA, N = 4–12, except for the gentamicin dose-response curves for BA-9, BA-10, BA-11, and BA-13, where N = 2 for the gentamicin-only groups. We are still confident in the data for these groups, based on the additional gentamicin data shown here and the data in Supplementary Figure S1. Bars are ± SEM. Refer to Table 1 for statistics.