Silicon incorporated tacrine: design, synthesis, and evaluation of biological and pharmacokinetic parameters.

ABSTRACT: Tacrine, an orally bioavailable cholinesterase inhibitor, was previously used to treat Alzheimer's disease but was withdrawn due to hepatotoxicity. The unique structural features of tacrine have once again captured the interest of medicinal chemists. However, the blood-brain barrier (BBB) permeability hampered the development of the majority of its new analogs. Herein, we employed a silicon switch approach for improving the BBB permeability of CNS drugs with tacrine as a tool compound. The replacement of C2 methylene of tacrine with dimethyl silicon yielded 'sila-tacrine' that inhibits acetylcholinesterase as well as butyrylcholinesterase with IC₅₀ values of 3.18 and 6.09 μM, respectively. Sila-tacrine competitively inhibits acetylcholinesterase while it is a non-competitive inh

SUBMITTER: Kulkarni AS 

PROVIDER: S-EPMC11959489 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature