PMID- 28687235
OWN - NLM
STAT- MEDLINE
DCOM- 20180319
LR  - 20180329
IS  - 1878-5867 (Electronic)
IS  - 0039-128X (Linking)
VI  - 125
DP  - 2017 Sep
TI  - Synthesis and evaluation of 26-amino acid methyl ester substituted sarsasapogenin 
      derivatives as neuroprotective agents for Alzheimer's disease.
PG  - 93-106
LID - S0039-128X(17)30114-9 [pii]
LID - 10.1016/j.steroids.2017.06.013 [doi]
AB  - Sarsasapogenin, extracted from Anemarrhena asphodeloides Bunge., has been 
      reported to protect neurons from H(2)O(2)-induced damage. In the current study, 
      four series of 26-amino acid methyl ester substituted sarsasapogenin derivatives 
      (5a-5e, 5f-5j, 6a-6e and 7a-7e) were synthesized and tested for neuroprotective 
      activity by evaluating their neuroprotective ratio against SH-SHY5Y cell lines. 
      Studies showed that most of the target compounds displayed better neuroprotective 
      effects than that of sarsasapogenin. Structure-activity relationship analysis 
      suggested that 3-methoxy derivatives (5f-5j) were more potent than other series 
      and the phenylalanine methyl ester moiety at C-26 was important for exhibiting 
      apparent neuroprotective activity. It was worth noting that compound 5h exhibited 
      optimal neuroprotective activity (102.2%) compared with sarsasapogenin (27.3%) 
      and trolox (40.5%), and this encouraged us to investigate the cellular mechanism 
      of 5h further. Our investigation revealed that 5h could attenuate 
      H(2)O(2)-induced cell damage by inhibiting the expression of cleaved poly 
      (ADP-ribose) polymerase (PARP) and cleaved caspase-3 as well as rescuing the 
      downregulation of brain-derived neurotrophic factor (BDNF) and its tyrosine 
      receptor kinase B (TrkB). Taken together, these results suggest that the 
      representative compound 5h is a profound lead compound for further investigation 
      and the sarsasapogenin skeleton could be a promising structural template for the 
      development of new anti-Alzheimer drug candidates.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Wang, Ze-Dan
AU  - Wang ZD
AD  - School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 
      Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based 
      Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical 
      University, Shenyang 110016, People's Republic of China.
FAU - Yao, Guo-Dong
AU  - Yao GD
AD  - School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 
      Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based 
      Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical 
      University, Shenyang 110016, People's Republic of China.
FAU - Wang, Wei
AU  - Wang W
AD  - School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 
      Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based 
      Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical 
      University, Shenyang 110016, People's Republic of China.
FAU - Wang, Wen-Bao
AU  - Wang WB
AD  - School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 
      Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based 
      Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical 
      University, Shenyang 110016, People's Republic of China.
FAU - Wang, Shao-Jie
AU  - Wang SJ
AD  - Key Laboratory of Structure-Based Drug Design & Discovery (Ministry of 
      Education), Shenyang Pharmaceutical University, Shenyang 110016, People's 
      Republic of China; School of Pharmaceutical Engineering, Shenyang Pharmaceutical 
      University, Shenyang 110016, People's Republic of China. Electronic address: 
      sjwang_99@163.com.
FAU - Song, Shao-Jiang
AU  - Song SJ
AD  - School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 
      Shenyang 110016, People's Republic of China; Key Laboratory of Structure-Based 
      Drug Design & Discovery (Ministry of Education), Shenyang Pharmaceutical 
      University, Shenyang 110016, People's Republic of China. Electronic address: 
      songsj99@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170705
PL  - United States
TA  - Steroids
JT  - Steroids
JID - 0404536
RN  - 0 (Amino Acids)
RN  - 0 (Esters)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Spirostans)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - CFS802C28F (sarsasapogenin)
SB  - IM
MH  - Alzheimer Disease/*pathology
MH  - Amino Acids/*chemistry
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Chemistry Techniques, Synthetic
MH  - Esters/*chemistry
MH  - Humans
MH  - Hydrogen Peroxide/pharmacology
MH  - Inhibitory Concentration 50
MH  - Neuroprotective Agents/*chemical synthesis/chemistry/*pharmacology
MH  - Spirostans/*chemical synthesis/chemistry/*pharmacology
OTO - NOTNLM
OT  - Alzheimer' disease
OT  - Amino acid methyl ester
OT  - Neuroprotection
OT  - Sarsasapogenin derivatives
EDAT- 2017/07/09 06:00
MHDA- 2018/03/20 06:00
CRDT- 2017/07/09 06:00
PHST- 2017/03/28 00:00 [received]
PHST- 2017/06/02 00:00 [revised]
PHST- 2017/06/29 00:00 [accepted]
PHST- 2017/07/09 06:00 [pubmed]
PHST- 2018/03/20 06:00 [medline]
PHST- 2017/07/09 06:00 [entrez]
AID - S0039-128X(17)30114-9 [pii]
AID - 10.1016/j.steroids.2017.06.013 [doi]
PST - ppublish
SO  - Steroids. 2017 Sep;125:93-106. doi: 10.1016/j.steroids.2017.06.013. Epub 2017 Jul 
      5.