Design and synthesis of D-ring steroidal isoxazolines and oxazolines as potential antiproliferative agents against LNCaP, PC-3 and DU-145 cells

• Novel steroidal isoxazolines and oxazolines screened for their anticancer activity.
• Analogs have promising anticancer activity against prostate cancer.
• The synthesis provides new avenues for steroid heterocyclization.
• Results are of prime importance for medicinal chemists and chemical biologists.
• Study provides new insights into steroid action and pharmacological potential.

Two series of novel steroidal isoxazolines and oxazolines were synthesized through different routes from dehydroepiandrosterone acetate and pregnenolone acetate, respectively. The synthesis of the analogs of both series is multistep and proceeds in good overall yields. While the key step in the synthesis of former is the cycloaddition of aromatic nitrile oxides across α,β-unsaturated olefins, it is the condensation of α,β-azidoalcohols with aromatic aldehydes in the later. Compounds of both the series were tested for their cytotoxic activities against LNCaP, PC-3 and DU-145 prostate cancer cell lines. Amongst all the compounds of both the series screened for their prostate cancer activity, compound 6a, 6e and 12a are the most active especially against LNCaP and DU-145 cancer cell lines.

Figure optionsDownload as PowerPoint slide