No abstract

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.

Four isomeric dehydroepiandrosterone- and pregnenolone-based N-alkynylaminosteroids were synthesized and tested in vitro for inhibition of heterologously expressed CYP17A1. The highest inhibitory activity was observed when the optimal number of side chain atoms was met. The conjugate based on pregnenolone containing an N-propynyl moiety was found to interefere with enzymatic activity most effectively and consistently in the micromolar range.

No abstract

A 3-acetyl analogue of 5-hydroxyindole was synthesised and evaluated for its effects on rat C6 glioma cell functions. It was found that 3-acetyl-5-hydroxy-2-methylindole at 10 μmol/L led to a sharp reduction of mitochondrial membrane potential, induction of autophagy and decrease of proliferation of C6 glioma cells. The compound’s effect was comparable to that of rotenone, an inhibitor of cell respiration.