New 3ß-hydroxysteroid-indolamine conjugates: Design, synthesis and inhibition of C6 glioma cell proliferation.

ABSTRACT

Four novel indole steroids based on dehydroepiandrosterone (IS-1), estrone (IS-2) and pregnenolone (IS-3) were obtained and studied for their ability to inhibit C6 glioma proliferation. A reduction in cell proliferation by 52 ± 13% was observed for IS-1 at 10 µM, whereas IS-3 and abiraterone acetate at 10 µM caused a 36 ± 8% decrease. Surprisingly, the cellular effects reported for abiraterone, namely, cytochrome P450 CYP17A1 inhibition and endoplasmic reticulum stress were not detected for IS-1. However, both abiraterone and IS-1 significantly increased glutathione levels. Docking studies predicted good affinity of IS-1 to liver X receptors and regulatory protein Keap1, which are proposed to be involved in the compounds' antiproliferative activity.