Tolserine ligand of proteins in family: ACHE, BCHE
References:
Search PubMed for references concerning: Tolserine
Title: Kinetics of human acetylcholinesterase inhibition by the novel experimental Alzheimer therapeutic agent, tolserine Kamal MA, Greig NH, Alhomida AS, Al-Jafari AA Ref: Biochemical Pharmacology, 60:561, 2000 : PubMed
Characterization of the kinetic parameters of tolserine, a novel acetylcholinesterase (AChE) inhibitor of potential in the therapy of Alzheimer's disease, to inhibit purified human erythrocyte AChE was undertaken for the first time. An IC(50) value was estimated by three methods. Its mean value was found to be 8.13 nM, whereas the IC(100) was observed to be 25.5 nM as calculated by single graphical method. The Michaelis-Menten constant (K(m)) for the hydrolysis of the substrate acetylthiocholine iodide was found to be 0.08 mM. Dixon as well as Lineweaver-Burk plots and their secondary replots indicated that the nature of the inhibition was of the partial non-competitive type. The value of K(i) was estimated as 4.69 nM by the primary and secondary replots of the Dixon as well as secondary replots of the Lineweaver-Burk plot. Four new kinetic constants were also investigated by polynomial regression analysis of the relationship between the apparent K(i) (K(Iapp)) and substrate concentration, which may open new avenues for the kinetic study of the inhibition of several enzymes by a wide variety of inhibitors in vitro. Tolserine proved to be a highly potent inhibitor of human AChE compared to its structural analogues physostigmine and phenserine.
Title: Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer's disease Yu Q, Holloway HW, Utsuki T, Brossi A, Greig NH Ref: Journal of Medicinal Chemistry, 42:1855, 1999 : PubMed
Four novel analogues (8-11) of cymserine (2) were synthesized by methods similar to those recently developed for the total syntheses of N8-norphenserine (Yu, Q. S.; et al. J. Med. Chem. 1997, 40, 2895-2901) and N1,N8-bisnorphenserine (Yu, Q. S.; et al. J. Med. Chem. 1998, 41, 2371-2379). As our structure-activity studies predicted, these compounds are highly potent and selective inhibitors of human butyrylcholinesterase (BChE) and will test the novel hypothesis that BChE inhibitors are useful in the treatment of Alzheimer's disease. In a similar manner, the same modifications that provided BChE selectivity were applied to the acetylcholinesterase (AChE)-selective inhibitor, tolserine (5), to provide the novel tolserine analogues 12-15. As predicted, these modifications altered the AChE-selective action of tolserine (5) to favor a lack of cholinesterase enzyme subtype selectivity.
