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Novel series of tacrine-tianeptine hybrids: Synthesis, cholinesterase inhibitory activity, S100B secretion and a molecular modeling approach

2016; Elsevier BV; Volume: 121; Linguagem: Inglês

10.1016/j.ejmech.2016.06.025

1768-3254

Marco Antônio Ceschi, Jessie Sobieski da Costa, João Paulo Bizarro Lopes, Viktor Saraiva Câmara, Leandra Franciscato Campo, Antonio Borges, Carlos Alberto Gonçalves, Diogo O. Souza, Eduardo Luis Konrath, Ana L. M. Karl, Isabella Alvim Guedes, Laurent E. Dardenne,

Nicotinic Acetylcholine Receptors Study

Tianeptine was linked to various 9-aminoalkylamino-1,2,3,4-tetrahydroacridines using EDC·HCl/HOBt to afford a series of tacrine-tianeptine hybrids. The hybrids were tested for their ability to inhibit AChE and BuChE and IC50 values in the nanomolar concentration scale were obtained. AChE molecular modeling studies of these hybrids indicated that tacrine moiety interacts in the bottom of the gorge with the catalytic active site (CAS) while tianeptine binds to peripheral anionic site (PAS). Furthermore, the compounds 2g and 2e were able to reduce the in vitro basal secretion of S100B, suggesting its therapeutic action in some cases or stages of Alzheimer's disease.