In silico discovery of substituted pyrido[2,3-d]pyrimidines and pentamidine-like compounds with biological activity in myotonic dystrophy models
Fig 9
Subcellular distribution of MBNL1 and in vivo evaluation of therapeutic potential.
(A) Confocal images of co-localization of MBNL1 (green) and foci (red) in DM1 myoblasts. Cells were treated with compounds for 48 h; nuclei were counter-stained with DAPI (blue). 1% DMSO-treated DM1 myoblasts and normal myoblasts were used as controls. Images include 2x enlargement of selected nucleus. (B) Climbing assay performed on 30 adult male flies fed for five days with the indicated compound. Climbing velocity was significantly higher in flies receiving 40 μM compound 2–5 or 100 μM compound 1–3 compared to DM1-model flies receiving only 1% DMSO solvent carrier. The average climbing velocity for wild type flies is marked as a red line. Statistics were calculated using the Student's t-test (**p < 0.01, ***p < 0.001).