Synthesis and evaluation of a xanthone analogue as AKT protein inhibitor in skeletal muscle cells

GONZALEZ, A.; MENDIOROZ, P.; GERBINO, DARÍO C.; BUITRAGO, CLAUDIA G.

Mar del Plata, Buenos Aires

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Sociedad Argentina de Investigación Clínica (SAIC)

Akt is a crucial regulator of cell survival, growth and proliferation. Consequently, its inhibition is an attractive strategy to target diverse types of cancer. The objective of this study was to synthesize a xanthone analogue and explore 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 etherification of the hydroxyl at position 3 was performed by nucleophilic displacement with 1,5-dibromopentane and K2CO3/acetone. (3) Treatment with diethylamine in ethanol under reflux produced the compound used in the biological assays.Cell viability assays 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 showed that the compound did not have a significant effect on C2C12 cellular viability, while it decreased the number of viable RD cells after 24 hours of treatment, with a percentage of diminution (% ± SD) 48,4 ± 24,4, p