Fig. 1.

Similars of bufalin and lycorine inhibit human cardiac fibroblast (HCF) proliferation. a 15 similars of bufalin and 11 similars of lycorine were investigated for their inhibitory potential on HCF proliferation, determined by BrdU incorporation. 14 similars of bufalin were able to inhibit HCF proliferation in a dose-dependent manner, whereas only one similar of lycorine (lyco-s) showed inhibitory activity. Solid lines represent calculated dose–response for bufalin (blue), lycorine (red), working set (black) and remaining active similars (grey). Dashed line represents control and inactive compounds, and dotted lines show exemplary 95% confidence interval for bufalin (blue), lycorine (red) and lyco-s (black). n = 3–7 biological replicates, 6–7 technical replicates each. b Similars inhibit metabolic activity of HCF (determined by WST-1 assay) with comparable EC50s as seen for BrdU incorporation. Lines and colours as in a. n = 4 biological replicates, 3–4 technical replicates each. c In silico prediction suggests superior drug properties for bufalin similars of the working set, whereas lyco-s scored lower than lycorine in most categories. The anti-fibrotic drugs nintedanib and pirfenidone (used in idiopathic pulmonary fibrosis, IPF) are in a comparable range for most categories. d Analysis of chemical structure showed high similarity between bufalin and the chosen similars, but not lycorine and lyco-s. e Sites of modification of bufalin and lycorine similars. f Working set of similars was selected by combining BrdU and WST-1-derived EC50 with the in silico-derived prediction score. Bufalin, lycorine, and similars selected in the working set are highlighted. Approved IPF drugs nintedanib and pirfenidone are shown for comparison