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

• Published in: Natural product research 2021-11, Vol.35 (21), p.3985-3991
• Main Authors: Hong, Dongfeng, Ma, Yiming, Song, Siyao, Li, Na, Wang, Junru
• Format: Article
• Language: English
• Subjects: 17a-aza-D-homo-androster-3-esters; antiproliferative activity; Brine shrimp toxicity; N-alkylated 17a-aza-D-homo-an-droster -17-ones
• ISSN: 1478-6419; 1478-6427
• DOI: 10.1080/14786419.2020.1753049

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, N-alkylation and deprotection. All compounds were characterized by 1 H NMR, 13 C NMR and HRMS. The structure of 14 g 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 11 h, 11i, 11 m, 11 s, 14 b and 14 g exhibited excellent toxicity against brine shrimp with LC 50 values ranging from 5.34 to 16.89 μg/mL, and compounds 11 s and 14 g displayed significant cytotoxicity against HT29 cells and A549 cells with IC 50 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.