Design, synthesis, brine shrimp lethality and cytotoxicity of some novel 17a-aza-D-homo-androster-17-one derivatives
| Autor: | Na Li, Si-yao Song, Dongfeng Hong, Yiming Ma, Junru Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
biology
010405 organic chemistry Chemistry Organic Chemistry Brine shrimp Plant Science biology.organism_classification 01 natural sciences Biochemistry Combinatorial chemistry 0104 chemical sciences Analytical Chemistry Structure-Activity Relationship 010404 medicinal & biomolecular chemistry Design synthesis Animals Humans Steroids Lethality Artemia Cytotoxicity HT29 Cells |
| Zdroj: | Natural Product Research. 35:3985-3991 |
| ISSN: | 1478-6427 1478-6419 |
| DOI: | 10.1080/14786419.2020.1753049 |
| Popis: | 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 1H NMR, 13C 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 LC50 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 IC50 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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