SYNTHESIS AND EVALUATION OF A XANTHONE ANALOGUE AS A NEW AKT PROTEIN INHIBITOR IN SKELETAL MUSCLE CELLS

GONZALEZ AGUSTINA; MENDIOROZ PAMELA; GERBINO DARÍO; BUITRAGO C

Congreso; SAIC reunión anual; 2023

Akt is a crucial regulator of cell survival, growth and proliferation and in consequence, its inhibition is an attractive strategy for the treatment of diverse types of cancer. The aim of this study was the synthesis of a xanthone analogue and the investigation of its potential as an inhibitor of Akt activation (Akt phosphorylation) in normal and cancerous skeletal muscle cells.The xanthone analogue was synthesized in three steps: (1) 1,3-dihydroxyxanthone was obtained through the intermolecular condensation between salicylic acid and phloroglucinol using ZnCl2 and POCl3. (2) Selective Williamson etherification of the phenolic hydroxyl group at the C3 position was carried out by nucleophilic displacement with 1,5-dibromopentane in the presence of K2CO3 and dry acetone. (3) Amination of the bromopentyl-substituted intermediate with diethylamine in dry acetone at room temperature, resulted in the xanthone analogue, later used in biological and molecular assays. Cell viability assays were developed with Trypan blue stained technique on C2C12 and RD cell lines exposed to 1.0 µM of the xanthone analogue for 24 and 48 hours. The results did not show any significant effect on the viability of the C2C12 cells. However, the number of viable RD cells decreased after 24 hours of treatment, with a percentage reduction of 48.4% ± 24.4 (SD), p