Design, synthesis, brine shrimp lethality and cytotoxicity of some novel 17a-aza-D-homo-androster-17-one derivatives.

In this work, twenty-eight novel 17a-aza-D-homo-androster-17-one derivatives, which divided into two categories, were synthesized with commercial available starting material (dehydroepiandrosterone) via oximation reaction, Beckmann rearrangement, hydroxyl protection, -alkylation and deprotection. All compounds were characterized by H NMR, C NMR and HRMS. The structure of was also identified by X-ray single crystal diffraction. The bioactivities, brine shrimp toxicity and cytotoxicity, of all derivatives were tested. The results indicated that compounds , , , , and exhibited excellent toxicity against brine shrimp with LC values ranging from 5.34 to 16.89 μg/mL, and compounds and displayed significant cytotoxicity against HT29 cells and A549 cells with IC values of 9.70 μM and 8.85 μM, respectively. Structure-activity relationships are discussed based on the results obtained from our research, and some important determinants for further modification of steroids towards the development of novel drug candidates are identified.