کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2027549 | 1542706 | 2015 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the [3+2] cycloaddition reactions of azomethine ylides Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the [3+2] cycloaddition reactions of azomethine ylides](/preview/png/2027549.png)
• Spirooxindoles are privileged scaffolds in drug discovery.
• A series of novel steroidal spirooxindoles were synthesized.
• Most of these compounds exhibited moderate to good antiproliferative activity.
• Some of them were more potent than 5-FU.
• Compound 3d caused cell cycle arrest at G2/M phase and early apoptosis.
A series of novel steroidal spirooxindoles 3a–h were synthesized from pregnenolone in a high regioselective manner using the 1,3-dipolar cycloaddition as the key step. This protocol resulted in the formation of two C–C bonds, one C–N bond and the creation of one pyrrolidine ring and three contiguous stereocenters in a single operation. Biological evaluation showed that these synthesized steroidal spirooxindoles exhibited moderate to good antiproliferative activity against the tested cell lines and some of them were more potent than 5-FU. Among them, compounds 3e and 3f displayed the best antiproliferative activity against MCF-7 cells with the IC50 values of 4.0 and 3.9 μM, respectively. Flow cytometry analysis demonstrated that compound 3d caused the cellular apoptosis and cell cycle arrest at G2/M phase in a concentration-dependent manner. Docking results indicated that compound 3d fitted well into the MDM2 active site 1RV1 by interacting with Lys94 and Thr101 residues.
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Journal: Steroids - Volume 102, October 2015, Pages 92–100