Inhibition of Cholinesterase by Dialkylcarbamates
Abstract The pI50 index and separation coefficients of chosen 3-N,N-diethylaminophenyl-N′,N′-dialkylcarbamates were determined. Index pI50 (pI50 = negative logarithm of molar concentration of inhibitor inhibiting the enzyme activity by 50%) describes the effectiveness of the inhibitor. The rate of ability of the inhibitor to pass the blood-brain barrier is usually described by the separation coefficient in a system n-octanol/water (Kow). Obtained results were compared with pI50 and Kow of Exelon®, the commercially used drug against the Alzheimer’s disease.
Inhibition of acetylcholinesterase by 14 achiral and five chiral imidazole derivates.
Homological series of 14 achiral derivates and series of five chiral derivates of imidazole were tested in vitro as inhibitors of hydrolysis of acetylcholine using enzyme preparation of acetylcholinesterase from electric eel. The batch stirred reactor at 25 degrees C, pH 8 (phosphate buffer), ionic strength 0.11 M and catalytic activity of the enzyme preparation 0.14 U ml(-1) of the reaction mixture were used. The temporal dependences of actual concentrations of acetylcholine, choline and acetic acid were determined by an original HPLC method. For all used inhibitors, these time dependences conform with the probability of more than 90% to the model of competitive irreversible inhibition. All kinetic constants including k(3) defining the rate of inhibition (0.38-5.3M(-1)s(-1)) and qualified estimation of the absolute acetylcholinesterase concentration in the reaction mixture (40-110 nM) were determined.
Towards a Formalisation of Justification and Justifiability
We introduce the logic QKD S which is a normal multi-modal logic over finitely many modalities that additionally supports bounded quantification of modalities. An important feature of this logic is that it allows to quantify over the information components of systems and, hence, can be used to derive justifications. We compare the proposed logic with Artemov’s justification logic and also report on a prototypical implementation of a satisfiability solver of this logic and show some examples.