Naslov
Carbamate derivatives of short-acting bronchodilator albuterol inhibits human acetylcholinesterase and butyrylcholinesterase

Autori
Bosak, Anita ; Knežević, Anamarija ; Zlatić, Katarina ; Kerep, Robert ; Kovarik, Zrinka

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

Izvornik
Book of Abstracts of the 10th Congress of Toxicology in Developing Countries and 12th Congress of the serbian Society of Toxicology / - , 2018, 114-114

Skup
10th Congress of Toxicology in Developing Countries (CTDC 10) ; 12th Serbian Congress of Toxicology

Mjesto i datum
Beograd, Srbija, 18.04.2018. - 21.04.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cholinesterase, selectivity, monocarbamate, biscarbamate, prodrug

Sažetak
Novel synthesised biscarbamate and monocarbamate derivatives of the short-acting bronchodilator albuterol (biscalb) resemble the structure of biscarbamate bambuterol, whose bioconversion to the bronchodilator terbutaline in an organism is enabled through the inhibition of butyrylcholinesterase (BChE). Bambuterol’s high therapeutic index is associated with an extremely selective BChE inhibition compared to acetylcholinesterase (AChE). We determined the inhibition potency of biscalb and monocalb toward human BChE and AChE to evaluate their selectivity. Both carbamates proved to be potent inhibitors of both cholinesterases with ki constants within 103-105 M-1min-1. Biscalb and monocalb inhibited AChE only 10 times slower than they did BChE, meaning that the selectivity of both carbamates was very poor compared to the 20, 000 times faster inhibition of BChE determined for bambuterol. Therefore, the novel compounds lack potential for prodrug development in analogy with bambuterol. However, due to their inhibition potency, these novel carbamates could be considered structural and functional lead compounds for the design of new compounds, whose primary action would be inhibition of cholinesterases, like pesticides or neurodegenerative disease drugs. Supported by CSF Grant no. 4307.

Izvorni jezik
Engleski

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