Synthesis And Biological Evaluation Of 17β-(P-substituted-1-phenyl-4-formyl-3-pyrazolyl)androst-5-ene-3β-OL Derivatives

Steroids as an important class of organic compounds which bear vital physiologic functions in organism, nowadays more and more researchers are interested in the steroids owing to its special structure characteristics and extensive biological activities which contain anticancer, anti-inflammatory, antibacterial and insecticidal activity. In order to seek novel and more potent bioactivities researchers focus on structure modification of these compounds via organic synthesis, in which ring system expansion that contains heteroatoms is the main stream especially constructing the heterocycles. For further study and analysis the structure-activity relationship of the steroidal derivatives modified with heterocycle rings and select more active compounds, we designed, synthesized a series of steroidal pyrazoles and their bioactivities were tested, with the following results:(1). Synthetic route: The synthetic procedure which commenced with pregnenolone as starting material, phenylhydrazone derivatives were obtained under the catalyst of acetic acid and cyclization through the Vilsmeier Reaction followed by hydrolysis, Borch Reduction, reduction and esterification to form the title derivatives which include 39 derivatives and their structures were characterized by 1H-NMR、13C-NMR、DEPT 135 o, the skeleton of the key intermediate was confirmed via single crystal diffraction. And there were no reports from literature of all synthesized compounds.(2) Bioactivities: The results of brine shrimp lethality proved that the aromatic amine derivatives were more efficient than the fatty amine derivatives, and the effective compounds 5.3, 5.7, 5.12, 5.13, 5.14, 5.15, 5.16, 5.22, 5.23, 5.27 their LC50 ranged from 8.16 μg/mL to 15.62 μg/mL. Antibacterial activity was carried out using the filter paper method and 6 kinds bacteria that contained Bacillus cereus, Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Pseudomonas solanacearum, Pseudomonas syringae pv.actinidiae were tested the results indicated that fatty amine derivatives 5.1, 5.2, 5.10, 5.19 and compound 6.1 exhibited a high degree of activity towards some of these bacteria. All the derivatives were tested their antiproliferation effects on the tumor cell lines including A549(human alveolar adenocarcinoma cell lines), Hela(human cervical cancer cell lines),MCF-7(human breast adenocarcinoma cell line) and HepG2(human liver hepatocellular carcinoma cell line).Compounds 5.1, 5.10, 5.19 and 6.1 showed preferable cytotoxic activity against A549、Hela、MCF7 cell lines their IC50 were ranged from 0.91 μM to 5.44 μM,but all the derivatives exhibited weak cytotoxic activity against HepG2 cell lines.