Naslov
Synthesis and evaluation of fluorinated Cinchona alkaloids as cholinesterases inhibitors

Autori
Ramić, Alma ; Hrenar, Tomica ; Matošević, Ana ; Bosak, Anita ; Primožič, Ines

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book of the 16th International Symposium on Cholinergic Mechanisms, Rehovot, Izrael / - Rehovot, 2019, 89-89

Skup
16th International Symposium on Cholinergic Mechanisms

Mjesto i datum
Reẖovot, Izrael, 08.12.2019. - 12.12.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cinchonidine, cinchonine, cholinesterases inhibitors

Sažetak
Cinchona alkaloids are natural products isolated from the bark of the Cinchona tree and the most known are quinine, quinidine, cinchonine and cinchonidine. These alkaloids and their derivatives are used in organic chemistry as chiral organocatalysts in asymmetric synthesis and as chiral agents in different chromatographic techniques. Also, they possess a wide variety of biological properties like anti-malarial, anti- inflammatory and anti-arrhythmic ones and recently they have been identified as human cholinesterase inhibitors. We synthesized seven quaternary derivatives of cinchonine and their corresponding pseudo-enantiomeric cinchonidine where the quaternization of quinuclidine nitrogen atom was achieved with differently substituted benzyl groups bearing fluorine atom(s) in different positions. All synthesized compounds reversibly inhibited the activity of both human butyrylcholinesterase and human acetylcholinesterase, with inhibition constants (Ki) in the range of 0.075-69 μM. All compounds were butyrylcholinesterase-selective inhibitors with up to 533 times higher affinity for butyrylcholinesterase compared to acetylcholinesterase. Generally, both cholinesterases were stereoselective to cinchonidines. Supported by the Croatian Science Foundation, Projects No. IP-2016-06- 3775 ADESIRE and IP-2018- 01-7683 AnalyseBChE.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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