| Title : Dual inhibitors of butyrylcholinesterase and histone deacetylase 6 for the treatment of Alzheimers disease: design, synthesis, and biological evaluation - Lv_2025_Bioorg.Med.Chem__118219 |
| Author(s) : Lv B , Wang Z , Wang Q , Xu Z , Tang J , Pei Y , Bian Y , Sun H , Chen Y |
| Ref : Bioorganic & Medicinal Chemistry , :118219 , 2025 |
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Abstract :
To address the multifactorial pathology of Alzheimers disease (AD), eighteen butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) dual inhibitors were designed, synthesized, and biologically evaluated. Through structureactivity relationship studies, compound 17 emerged as the most potent candidate, with IC50 value of 0.3nM for human BChE and 56.7nM for HDAC6. This compound demonstrated favorable safety profiles, drug-like properties, and significant neuroprotective effects in vitro. In a mouse model of scopolamine-induced cognitive impairment, 17 (10mg/kg) exhibited excellent safety and markedly improved cognitive deficits. These findings highlight compound 17 as a promising BChE/HDAC6 dual inhibitor, supporting its further development as a potential therapeutic agent for AD. |
| PubMedSearch : Lv_2025_Bioorg.Med.Chem__118219 |
| PubMedID: |
| Inhibitor | S11-1014-hydroxamide-cpd17 |
Lv B, Wang Z, Wang Q, Xu Z, Tang J, Pei Y, Bian Y, Sun H, Chen Y (2025)
Dual inhibitors of butyrylcholinesterase and histone deacetylase 6 for the treatment of Alzheimers disease: design, synthesis, and biological evaluation
Bioorganic & Medicinal Chemistry
:118219
Lv B, Wang Z, Wang Q, Xu Z, Tang J, Pei Y, Bian Y, Sun H, Chen Y (2025)
Bioorganic & Medicinal Chemistry
:118219