Atranorin is a novel potential candidate drug for treating myelodysplastic syndrome

Abstract

This work is devoted to the study of biocompatibility, cyto- and genotoxicity, mechanism of action and prospects for the use of atranorin, which is an AKT kinase inhibitor, for the treatment of myelodysplastic syndrome. Atranorin was isolated by preparative flash chromatography; identification was carried out by UV, IR, and NMR spectroscopy, mass spectrometry, and elemental analysis. Biocompatibility studies included studies of haemocompatibility, genotoxicity, antioxidant activity, cytotoxicity against ECV340 and HEK293 cell lines. Computer modelling of the interaction of atranorin with AKT kinase was carried out using docking followed by molecular dynamics of the resulting complexes; the ADMET properties of atranorin were also calculated. Flow cytometry included analysis of the expression level of PD-L1 and TIM-3 in the presence of atranorin on THP-1, Mono-Mac-1 and KG-1 cell lines, as well as human bone marrow cells.