Diagnostic and chemotherapeutic potential of selective 5and#945; reductase inhibitor in experimentally induced glioma in rats

Abstract

Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options, necessitating the identification of new therapeutic targets. 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. The present study reports the successful synthesis and direct radiolabeling of 5and#945;,6and#946;-dibromo-17-oximino-androstan-3and#946;-ylphenylacetate with and#8313;and#8313;and#7504;Tc, achieving a radiochemical purity exceeding 80%. The radiolabeled complex demonstrated high stability under both in vitro and in vivo conditions. In silico analysis revealed a higher binding affinity of the synthesized compound toward 5and#945;-reductase compared to the standard drug finasteride. In vitro studies showed that the compound significantly inhibited C6 glioma cell proliferation, migration, and invasion, exhibiting superior inhibitory potential relative to finasteride. In vivo investigations further demonstrated enhanced tumor-targeting ability of the radiopharmaceutical, highlighting its promise for diagnostic imaging and therapeutic applications. Elevated levels of dihydrotestosterone (DHT) and 5and#945;-reductase observed in glioma-bearing rats were significantly reduced following treatment with the synthesized compound, indicating its role in glioma suppression. Overall, these findings establish the potential of 5and#945;,6and#946;-dibromo-17-oximino-androstan-3and#946;-ylphenylacetate as an effective agent for glioma management and provide a strong basis for further molecular mechanistic and translational studies. newline