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We synthesized a group of original compounds, which combine in one molecule \u03b3-carboline fragment of dimebon and phenothiazine core of methylene blue (MB) linked by 1-oxo- and 2-hydroxypropylene spacers. Inhibitory activity of the conjugates toward acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and structurally close to them carboxylesterase (CaE), as well their binding to NMDA-receptors were evaluated<jats:italic>in vitro<\/jats:italic>and<jats:italic>in silico<\/jats:italic>. These newly synthesized compounds showed significantly higher inhibitory activity toward BChE with IC<jats:sub>50<\/jats:sub>values in submicromolar and micromolar range and exhibited selective inhibitory action against BChE over AChE and CaE. Kinetic studies for the 9 most active compounds indicated that majority of them were mixed-type BChE inhibitors. The main specific protein-ligand interaction is \u03c0-\u03c0 stacking of phenothiazine ring with indole group of Trp82. These compounds emerge as promising safe multitarget ligands for the further development of a therapeutic approach against aging-related neurodegenerative disorders such as Alzheimer and\/or other pathological conditions.<\/jats:p>","DOI":"10.1038\/srep13164","type":"journal-article","created":{"date-parts":[[2015,8,18]],"date-time":"2015-08-18T09:31:46Z","timestamp":1439890306000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Conjugates of \u03b3-Carbolines and Phenothiazine as new selective inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer Disease"],"prefix":"10.1038","volume":"5","author":[{"given":"Galina F.","family":"Makhaeva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofya V.","family":"Lushchekina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia P.","family":"Boltneva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir B.","family":"Sokolov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir V.","family":"Grigoriev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga G.","family":"Serebryakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina A.","family":"Vikhareva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey Yu.","family":"Aksinenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George E.","family":"Barreto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gjumrakch","family":"Aliev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey O.","family":"Bachurin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,8,18]]},"reference":[{"key":"BFsrep13164_CR1","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1111\/j.1365-2125.2011.04134.x","volume":"73","author":"S Salomone","year":"2012","unstructured":"Salomone, S., Caraci, F., Leggio, G. 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