Three (―)-cytisine derivatives and 1-hydroxyquinopimaric acid as acetylcholinesterase inhibitors

Abstract

In vitro acetylcholinesterase (AChE) inhibition was studied using novel derivatives of (―)-cytisine derivatives N-allylcytisine-12-carbamide (A-63), cytisine-12-carbamide (A-36), N-1-adamantylcytisine-12-thiocarbamide (U-12), and 1-hydroxyquinopimaric acid (U-201). Inhibition of acetylcholinesterase with compound A-63 was described as mixed inhibition. Substances (A-36) and (U-201) acted as competitive inhibitors with Ki equal to 6.71 mM and 3.89 mM, respectively, while (U-12) behaved as an uncompetitive inhibitor with Ki at 0.07 mM. The IC50 values were estimated at 1.47, 13.73, 3.39, and 7.81 mM, respectively. According to toxicity assessment, compound A-63 was non-toxic; it did not affect A. salina viability at a concentration less than 1000 ppm, while at 1000 ppm, only 3% mortality was observed. Mortality of A. salina was less than 50% in the same concentration range for the other three compounds that allow classifying them as moderately toxic. Although tested compounds have the characteristics of weak inhibitors, they could be useful as protectors against potent organophosphates. The present research may be fundamental to the design of new substances for acetylcholinesterase inhibition. Keywords: Acetylcholinesterase inhibition, (-)-Cytisine derivatives, 1-Hydroxyquinopimaric acid, Toxicity on Artemia salina model