title: Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as neuroprotective agents.
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.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhangjiang High-Tech Park, Shanghai, PR China.
authors.forename: Cheng-Shi
authors.initials: CS
authors.lastname: Jiang
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Guo
authors.forename: Jing-Xu
authors.initials: JX
authors.lastname: Gong
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhu
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Yue-Wei
authors.initials: YW
authors.lastname: Guo
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D011284:Pregnenolone; D006861:Hydrogen Peroxide; D005947:Glucose; D010100:Oxygen