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group might be required for the neuroprotective effects against
OGD-induced neurotoxicity in SH-SY5Y cells.
In summary, a series of 21-arylidenepregnenolone derivatives
was synthesized and biologically evaluated. The bioassay results
indicated that several synthetic derivatives displayed potent
neuroprotective effects in different screening models, e.g., com-
pounds 2b, 3a, 3b, and 3s showing significant activities against
Ab25–35-induced neurotoxicity in PC12 cells, 2b showing significant
activities against H2O2-induced neurotoxicity in PC12 cells, while
2g, 3b, and 3e showing potent protection against OGD insult. The
results observed in present studies indicated that introduction of
an arylidene group into steroidal nucleus probably play an essen-
tial role in neuroprotective activity, and the formation of epoxy
group at C-5,6 could be also important for the neuroprotective
activity in some degree. Our preliminary structure–activity rela-
tionship (SAR) study provided information that could be useful
for the design of novel steroidal neuroprotective drug candidates
or leads. Further studies to improve neuroprotective activity and
clarify the neuroprotective mechanism of this class of compounds
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Acknowledgments
This research work was financially supported by the Natural
Science Foundation of China (Nos. 21072204, 81072572,
and 21021063), the National Marine ‘863’ Project (No.
2011AA09070102), the SKLDR/SIMM Projects (Nos. SIMM1105KF-
04, simm0907KF and SIMM1106KF-11), and was partially funded
by the EU 7th Framework Programme-IRSES Project (2010–2014),
the STCSM Project (No. 10540702900), the Hungarian–Chinese
Intergovernmental S&T Cooperation Programme (2009–2011), and
CAS grants (KSCX2-YW-R-18 and KSCX2-EW-R-15).
2 h and then suffered cell injury by 1 lM Ab25–35 or 300 lM H2O2 for another
24 h; SH-SY5Y cells, pretreated with compounds for 2 h, were exposed to 1 mg/
mL OGD for 1 h and cultured for another 24 h under normal condition and SH-
SY5Y cells cultured with glucose under normal condition were served as
control. Cell viability was evaluated by incubating with 0.5 mg/mL 3-[4,5-
dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) for 3 h under
5% CO2/95% air at 37 °C. Media were replaced with 100 ll DMSO, then
absorbance was read at 490 nm. Data were analyzed by one-way analysis of
variance (ANOVA) and expressed as means SD with P <0.05 as significance.
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Supplementary data
Supplementary data associated with this article can be found, in
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