1365727-72-5Relevant academic research and scientific papers
Efficient synthesis of novel antiproliferative steroidal spirooxindoles via the [3+2] cycloaddition reactions of azomethine ylides
Yu, Bin,Sun, Xiao-Nan,Shi, Xiao-Jing,Qi, Ping-Ping,Zheng, Yi-Chao,Yu, De-Quan,Liu, Hong-Min
, p. 92 - 100 (2015)
Abstract 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.
Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as neuroprotective agents
Jiang, Cheng-Shi,Guo, Xian-Jun,Gong, Jing-Xu,Zhu, Ting-Ting,Zhang, Hai-Yan,Guo, Yue-Wei
supporting information; experimental part, p. 2226 - 2229 (2012/05/04)
A series of 21-arylidenepregnenolone derivatives and their corresponding epoxides were synthesized. The neuroprotective effects of these steroidal compounds against amyloid-β25-35 (Aβ25-35)- and hydrogen peroxide (H2O2)-induced neurotoxicity in PC12 cells, and oxygen-glucose deprivation (OGD)-induced neurotoxicity in SH-SY5Y cells were evaluated. The bioassay results indicated that several 3β-pregn-21-benzylidene-20-one derivatives displayed potent in vitro neuroprotective effects in different screening models, for example, compounds 2b, 3a, 3b, and 3s showing significant activities against Aβ 25-35-induced neurotoxicity in PC12 cells, 2b showing significant activities against H2O2-induced neurotoxicity in PC12 cells, and 2g, 3b, and 3e showing potent protection against OGD insult. The results suggested that introduction of an arylidene group into steroidal nucleus played an important role in neuroprotective activity, while the formation of epoxy group at C-5,6 could be also important for the neuroprotective activity in some degree. The pharmacological data reported here are helpful for the design of novel steroidal neuroprotective candidates.
