Evaluation of Therapeutic Potential of a Selective 5α-reductase Inhibitor against Glioblastoma: Molecular Docking and In Vitro Insights.

Various experimental and clinical reports highlight the increased expression of androgen receptors (AR) in Glioblastoma (GBM) biopsies which indicates that targeting the ARs might be a rational treatment solution for glioma. In the same light, the present study aimed to synthesise a steroidal androsten analogue and evaluate its specificity and therapeutic potential in C6 glioma cell lines. Taking into consideration the 5α reductase inhibitory activity of the reported esters and based on the observation of the importance of the electronegative group at C-6 of the steroidal skeleton, a steroidal androsten analogue viz: 5α, 6β-dibromo derivative of 17-Oxo-5-androstane-3β-yl ester was synthesised and assessed for its specificity in targeting AR in in-silico and in vitro conditions. Further, the synthesised compound was assessed for its therapeutic potential by performing cytotoxicity assay, wound healing migration assay and transwell Cell Invasion Assay. High D score in the in-silico study indicated specificity and higher binding affinity of the synthesised compound towards androgen receptor as compared to the reference drug finasteride. MTT assay performed in C6 rat glioma cell line showed significant cytotoxicity with IC values of 23.3 µM at 24 h and 11.18 µM at 48 h for 5α, 6β-dibromo-17-oxo-androstan-3βyl-phenylacetate. The IC values were significantly higher for the reference drug, finasteride (24 h:59.9 µM and 48 h:26 µM). Further, the synthesized drug significantly decreased cell migration and invasion at a lower concentration than finasteride, which was ineffective even at IC value. To conclude, the preliminary finding on the synthesised steroidal androsten analogue shows its promising potential to be exploited further for its therapeutic potential and effectiveness in animal models.