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A novel class of small molecule inhibitors with radioprotective properties

Publication at Faculty of Medicine in Hradec Králové |
2020

Abstract

The goal of this study was to develop novel radioprotective agents targeting the intrinsic apoptotic pathway and thus decreasing the radiation-induced damage. For that purpose, we designed, synthesized and analyzed ten new compounds based on the 1-(4-(2-hydroxyethyl)piperazin-l-yl)-3-phenoxypropan-2-ol leading structure.

The cytotoxicity of the newly synthesized substances was tested in vitro on cell lines derived from different progenitor cells by WST-1 proliferation assay. mTr test was utilized to assess half-maximal inhibitory concentrations and maximum tolerated concentrations of novel compounds in A-549 cells. Screening for radioprotective properties was performed using flow-cytometry in MOLT-4 cells exposed to Co-60 ionizing gamma radiation.

Selected candidates underwent in vivo testing in C57BI/6J mice having a positive impact on their immunological status. In summary, we report here promising compounds with radioprotective effect in vivo. (C) 2019 Elsevier Masson SAS.

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