CoChat
Sign Up
Cited by 27

The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.

Discovery of Potent Cholinesterase Inhibition-Based Multi-Target-Directed Lead Compounds for Synaptoprotection in Alzheimer’s Disease

Turgutalp, Bengisu, Bhattarai, Prabesh, Ercetin, Tugba, Luise, Chiara, Reis, Rengin, Gurdal, Enise Ece, Isaak, Andreas, Biriken, Derya, Dinter, Elisabeth, Sipahi, Hande, Schepmann, Dirk, Junker, Anna, Wünsch, Bernhard, Sippl, Wolfgang, Gulcan, Hayrettin Ozan, Kizil, Caghan, Yarim, Mine·2022·Journal of Medicinal Chemistry
DOI 10.1021/acs.jmedchem.2c01003
Open this paper in CoChat — free account

Abstract

Drug development efforts that focused on single targets failed to provide effective treatment for Alzheimer's disease (AD). Therefore, we designed cholinesterase inhibition (ChEI)-based multi-target-directed ligands (MTDLs) to simultaneously target AD-related receptors. We built a library of 70 compounds, sequentially screened for ChEI, and determined σ 1 R, σ 2 R, NMDAR-GluN2B binding affinities, and P2X7R antagonistic activities. Nine fulfilled in silico drug-likeness criteria and did not display toxicity in three cell lines. Seven displayed cytoprotective activity in two stress-induced cellular models. Compared to donepezil, six showed equal/better synaptic protection in a zebrafish model of acute amyloidosis-induced synaptic degeneration. Two P2X7R antagonists alleviated the activation state of microglia in vivo . Permeability studies were performed, and four did not inhibit CYP450 3A4, 2D6, and 2C9. Therefore, four ChEI-based lead MTDLs are promising drug candidates for synaptic integrity protection and could serve as disease-modifying AD treatment. Our study also proposes zebrafish as a useful preclinical tool for drug discovery and development.

Overview

Integrity signals

Registry

Crossref · 10.1021/acs.jmedchem.2c01003

Cites

13 of 13 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In zebrafish, several S2R modulators with polypharmacology demonstrated synaptoprotection in two stress-induced models of synaptic degeneration.

    “In zebrafish, several S2R modulators with polypharmacology, exhibiting activity on multiple targets, demonstrated synaptoprotection in two stress-induced models of synaptic degeneration in zebrafish [83].”

    From Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases (2023) · cites this paper as [83]

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 110

  1. Barrett K. E., 2018, Ganong’s Review of Medical Physiology
  2. 10.1101/cshperspect.a006189 · DOI · Paper page
  3. 10.1002/alz.12328 · DOI
  4. 10.37765/ajmc.2020.88482 · DOI
  5. 10.1159/000362926 · DOI
  6. 10.1186/s40035-018-0107-y · DOI
  7. 10.1001/jamainternmed.2021.4610 · DOI
  8. 10.1136/bmj.n3127 · DOI
  9. 10.18553/jmcp.2021.27.11.1613 · DOI
  10. 10.1002/med.20248 · DOI
  11. 10.1021/acschemneuro.8b00069 · DOI
  12. 10.2174/0929867326666181203124102 · DOI
  13. 10.2174/1570159X13666150716165726 · DOI · Paper page
  14. 10.1017/S1041610203008676 · DOI
  15. 10.1016/S0197-4580(04)80726-7 · DOI
  16. 10.1124/pr.109.002451 · DOI · Paper page
  17. 10.1016/S0165-6147(00)89070-7 · DOI
  18. 10.1016/j.neuint.2004.03.007 · DOI · Paper page
  19. 10.3233/JAD-150942 · DOI
  20. 10.1038/nrn2207 · DOI · Paper page
  21. 10.1016/j.brainresbull.2012.10.005 · DOI
  22. 10.1016/j.neuropharm.2016.07.037 · DOI
  23. 10.1016/j.neuropharm.2017.02.003 · DOI
  24. 10.1186/1742-2094-8-14 · DOI
  25. 10.1016/j.bbi.2013.09.008 · DOI
  26. 10.1016/j.neuro.2014.03.004 · DOI
  27. Gilbert P. E., 1976, J. Pharmacol. Exp. Ther., 197, 517
  28. 10.1016/0165-6147(92)90030-A · DOI
  29. 10.1016/0014-2999(89)90200-8 · DOI
  30. 10.1073/pnas.93.15.8072 · DOI
  31. 10.1006/bbrc.1996.1842 · DOI
  32. 10.1046/j.1471-4159.1998.70030922.x · DOI
  33. 10.1016/j.cell.2007.08.036 · DOI · Paper page
  34. 10.1007/978-3-319-50174-1_10 · DOI
  35. 10.2174/1871524910909030184 · DOI
  36. 10.1124/jpet.111.191189 · DOI
  37. 10.1016/j.expneurol.2013.04.009 · DOI
  38. 10.2174/156720206776875849 · DOI
  39. 10.1016/j.nbd.2013.10.010 · DOI
  40. 10.1093/brain/awu107 · DOI
  41. 10.1159/000440864 · DOI
  42. 10.1038/npp.2013.70 · DOI
  43. 10.1124/jpet.105.097394 · DOI
  44. 10.1016/S0304-3940(98)00943-4 · DOI
  45. 10.1093/hmg/ddw204 · DOI
  46. 10.1021/acsmedchemlett.1c00002 · DOI
  47. 10.1016/j.trci.2018.11.001 · DOI · Paper page
  48. 10.1002/alz.12302 · DOI · Paper page
  49. 10.1111/jnc.13917 · DOI · Paper page
  50. 10.2174/187152712803581137 · DOI
  51. 10.1073/pnas.0707370105 · DOI
  52. 10.1073/pnas.1002396107 · DOI
  53. 10.1080/14728222.2019.1575811 · DOI
  54. 10.1016/j.brainresbull.2018.07.016 · DOI
  55. 10.1016/j.neuroscience.2014.08.036 · DOI
  56. 10.1186/s12974-018-1205-6 · DOI
  57. 10.1111/bph.12314 · DOI
  58. 10.1124/jpet.114.218487 · DOI
  59. 10.1016/j.bmcl.2016.10.041 · DOI
  60. 10.1016/0014-2999(93)90147-A · DOI
  61. 10.1038/s41398-018-0201-z · DOI
  62. 10.1002/trc2.12295 · DOI · Paper page
  63. 10.1038/nchembio.2089 · DOI
  64. 10.1016/j.ejmech.2021.113838 · DOI
  65. 10.3390/molecules22122098 · DOI
  66. 10.1016/0014-2999(93)90147-A · DOI
  67. 10.1016/j.farmac.2005.06.014 · DOI
  68. 10.2174/1871520617666170412153604 · DOI
  69. 10.1016/j.cbi.2019.06.011 · DOI
  70. 10.1016/j.ejmech.2018.07.033 · DOI
  71. 10.1016/j.bmc.2013.01.038 · DOI
  72. 10.1016/j.ejmech.2014.06.073 · DOI
  73. 10.1016/0922-4106(92)90153-M · DOI
  74. 10.1016/0024-3205(95)00301-L · DOI
  75. 10.1016/j.jpba.2010.04.014 · DOI
  76. 10.1016/j.bmc.2011.04.002 · DOI
  77. 10.1124/mol.112.078568 · DOI
  78. 10.1038/nature10180 · DOI
  79. 10.14440/jbm.2017.136 · DOI
  80. 10.1517/17460441.2.6.799 · DOI
  81. 10.1186/s40169-017-0181-2 · DOI
  82. 10.1093/bioinformatics/btx491 · DOI
  83. 2019, Schrödinger Release 2019-4: QikProp
  84. 10.3389/fnagi.2017.00337 · DOI
  85. 10.1096/fj.01-0995fje · DOI
  86. 10.1016/j.cbi.2008.04.045 · DOI
  87. 10.1111/jnc.12319 · DOI
  88. 10.1016/j.ejmech.2019.07.012 · DOI
  89. 10.1371/journal.pone.0063583 · DOI
  90. 10.1007/s11307-011-0493-3 · DOI
  91. 10.1046/j.1471-4159.2002.01110.x · DOI
  92. 10.1007/s11302-017-9567-2 · DOI · Paper page
  93. 10.3390/ijms21113959 · DOI
  94. 10.3389/fendo.2012.00041 · DOI
  95. 10.3389/fncel.2018.00314 · DOI
  96. 10.1523/JNEUROSCI.23-08-03364.2003 · DOI
  97. 10.3791/56014 · DOI
  98. 10.1080/23262133.2017.1322666 · DOI
  99. 10.1007/s00401-022-02431-6 · DOI
  100. 10.4103/1673-5374.259609 · DOI
  101. 10.1016/0304-3940(95)11763-M · DOI · Paper page
  102. 10.1371/journal.pone.0209250 · DOI
  103. 10.1016/j.pnpbp.2008.06.011 · DOI
  104. 10.1371/journal.pone.0037989 · DOI
  105. 10.1021/acs.jmedchem.0c01192 · DOI
  106. 10.1002/glia.23001 · DOI · Paper page
  107. 10.1016/S0223-5234(03)00012-6 · DOI · Paper page
  108. 10.1021/jm001020e · DOI
  109. 10.1021/acs.jmedchem.0c00463 · DOI
  110. 10.1177/1087057104269731 · DOI

Cited by

Sorted by citations

Metadata

Authors
Turgutalp, B., Bhattarai, P., Ercetin, T., Luise, C., Reis, R., Gurdal, E. E., Isaak, A., Biriken, D., Dinter, E., Sipahi, H., Schepmann, D., Junker, A., Wünsch, B., Sippl, W., Gulcan, H. O., Kizil, C., & Yarim, M.
Affiliations
  • Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Yeditepe University, 34755 Istanbul, Turkey
  • German Centre for Neurodegenerative Diseases (DZNE), Helmholtz Association, 01307 Dresden, Germany
  • Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Eastern Mediterranean University, TRNC, via Mersin 10, 99628 Famagusta, Turkey
  • Department of Medicinal Chemistry, Institute of Pharmacy, Martin-Luther-Universität Halle-Wittenberg, 6099 Halle (Saale), Germany
  • Department of Toxicology, Faculty of Pharmacy, Yeditepe University, 34755 Istanbul, Turkey
  • European Institute for Molecular Imaging (EIMI), der Westfälischen Wilhelms-Universität, D-48149 Münster, Germany
  • Institute of Pharmaceutical and Medicinal Chemistry, University of Münster, D-48149 Münster, Germany
ORCID
Venue
Journal of Medicinal Chemistry
Publisher
American Chemical Society (ACS)
Published
2022-09-09
Volume
65
Issue
18
Pages
12292-12318
ISSN
  • 0022-2623
  • 1520-4804
DOI
10.1021/acs.jmedchem.2c01003
Cited by
27
References
13
Language
en
Licence
Funders
  • European Commission
  • T??rkiye Bilimsel ve Teknolojik Arastirma Kurumu (2219)
  • Helmholtz Association
  • Deutsches Zentrum f??r Neurodegenerative Erkrankungen
  • Clinician Scientist program Else Kr??ner Research College TU Dresden (060_1102)
  • Schaefer Research Scholars Award

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review