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@ARTICLE{Liang:291284,
      author       = {T. Liang and S. Liu and B. Dang and X. Luan and Y. Guo and
                      R. Steimbach$^*$ and A. Miller$^*$ and J. Hu and L. Lu and
                      P. Yue and R. Wang and M. Zheng and J. Gao and X. Yin and X.
                      Chen},
      title        = {{M}ultimechanism biological profiling of
                      tetrahydro-β-carboline analogues as selective {HDAC}6
                      inhibitors for the treatment of {A}lzheimer's disease.},
      journal      = {European journal of medicinal chemistry},
      volume       = {275},
      issn         = {0009-4374},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DKFZ-2024-01367},
      pages        = {116624},
      year         = {2024},
      abstract     = {With the intensive research on the pathogenesis of
                      Alzheimer's disease (AD), inhibition of HDAC6 appears to be
                      a potential therapeutic approach for AD. In this paper, a
                      series of tetrahydro-β-carboline derivatives with
                      hydroxamic acid group were fast synthesized. Among all, the
                      most potent 15 selectively inhibited HDAC6 with IC50 of 15.2
                      nM and markedly increased acetylated alpha-tubulin levels.
                      In cellular assay, 15 showed excellent neurotrophic effect
                      by increasing the expression of GAP43 and Beta-3 tubulin
                      markers. Besides, 15 showed neuroprotective effects in PC12
                      or SH-SY5Y cells against H2O2 and 6-OHDA injury through
                      activation of Nrf2, catalase and Prx II, and significantly
                      reduced H2O2-induced reactive oxygen species (ROS)
                      production. In vivo, 15 significantly attenuated zebrafish
                      anxiety-like behaviour and memory deficits in a SCOP-induced
                      zebrafish model of AD. To sum up, multifunctional 15 might
                      be a good lead to develop novel tetrahydrocarboline-based
                      agents for the treatment of AD.},
      keywords     = {Alzheimer's disease (Other) / HDAC6 inhibitor (Other) /
                      Multimechanism (Other) / Selectivity (Other) /
                      Tetrahydrocarboline (Other)},
      cin          = {A390},
      ddc          = {610},
      cid          = {I:(DE-He78)A390-20160331},
      pnm          = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
      pid          = {G:(DE-HGF)POF4-311},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38925015},
      doi          = {10.1016/j.ejmech.2024.116624},
      url          = {https://inrepo02.dkfz.de/record/291284},
}