In this work we examined the synthesized N-alkynyl-17-aminosteroids and N-alkynyl-20-aminosteroids (based on dehydroepiandrosterone and pregnenolone, respectively) for their effect on C6 rat glioma cell functions. At 10 μM, the compounds had an insignificant effect on C6 glioma mitochondrial membrane potential, but increased cell autophagy by 70-90%, comparable to the known autophagy inducer dexamethasone. Docking simulations predict a potential high-affinity interaction between N-alkynylaminosteroids and Keap1 and the Hedgehog pathway protein, Smoothened, which are involved in autophagy regulation. The possible mechanisms of observed processes are discussed.
Issledovano vliianie sintezirovannykh na osnove degidroépiandrosterona i pregnenolona N-alkinil-17-aminosteroidov i N-alkinil-20-aminosteroidov na funktsii kletok gliomy krysy linii S6. Ustanovleno, chto v kontsentratsii 10 mkM issledovannye N-alkinilaminosteroidy ne vliiaiut na mitokhondrial'nyĭ membrannyĭ potentsial. V analogichnykh usloviiakh N-alkinilaminosteroidy usilivaiut protsessy autofagii v kletkakh gliomy na 70-90%, chto bylo sopostavimo s aktivnost'iu izvestnogo induktora autofagii deksametazona. Komp'iuternyĭ doking struktur poluchennykh soedineniĭ pokazal vozmozhnost' affinnogo sviazyvaniia N-alkinilaminosteroidov s belkom Keap1 i belkom Smoothened signal'nogo puti Hedgehog, uchastvuiushchimi v reguliatsii autofagii. Obsuzhdaiutsia vozmozhnye mekhanizmy nabliudaemykh protsessov.
Keywords: alkynylaminosteroids; anticancer compounds; autophagy; glioma; mitochondria.