Influence of N-Alkynylaminosteroids on Mitochondrial Functioning and Autophagy in Glioma Cells

• Published in: Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Vol. 16; no. 3; pp. 246 - 252
• Main Authors: Panada, J. U., Klopava, V. A., Kulahava, T. A., Faletrov, Y. V., Frolova, N. S., Koran, S. V., Fomina, E. G., Shkumatov, V. M.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-09-2022; Springer Nature B.V
• Subjects: Autophagy; Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; Dehydroepiandrosterone; Dexamethasone; Glioma; Glioma cells; Medicinal Chemistry; Membrane potential; Mitochondria; Pregnenolone; glioma; autophagy; anticancer compounds; alkynylaminosteroids; mitochondria
• ISSN: 1990-7508; 1990-7516
• DOI: 10.1134/S199075082203009X

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The effect of the synthesized
N
-alkynyl-17-aminosteroids and
N
-alkynyl-20-aminosteroids (based on dehydroepiandrosterone and pregnenolone, respectively) on C6 rat glioma cell functions has been investigated. At 10 μM, the compounds had an insignificant effect on C6 glioma mitochondrial membrane potential, but increased cell autophagy by 70–90%; this effect was 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.