Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as neuroprotective agents

Bioorganic & Medicinal Chemistry Letters
Cheng-Shi JiangYue-Wei Guo

Abstract

A series of 21-arylidenepregnenolone derivatives and their corresponding epoxides were synthesized. The neuroprotective effects of these steroidal compounds against amyloid-β(25-35) (Aβ(25-35))- and hydrogen peroxide (H(2)O(2))-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 H(2)O(2)-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.

Citations

Mar 9, 2013·Journal of Agricultural and Food Chemistry·Gonggong HeChunbao Li
Feb 17, 2017·Bioorganic & Medicinal Chemistry Letters·Saransh Wales MauryaRakesh Maurya
May 29, 2018·Journal of Asian Natural Products Research·Cheng-Shi JiangJin-Hai Yu
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Vanessa BritoSamuel Silvestre

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