Donepezil-melatonin hybrids as butyrylcholinesterase inhibitors: Improving binding affinity through varying mode of linking fragments.

Hybrid inhibitors of acetyl- and butyrylcholinesterase are compounds that combine structural motifs of two different classical inhibitors, leading to a dual binding ligand. A rapidly growing collection of those compounds involves a wide diversity of structural motifs, but the way of linking two active fragments and its impact on the affinity toward cholinesterases usually remains beyond the extent of investigation. We present hereby a detailed analysis of this aspect using melatonin-donepezil hybrids.

Isoprenoid Alcohols are Susceptible to Oxidation with Singlet Oxygen and Hydroxyl Radicals.

Isoprenoids, as common constituents of all living cells, are exposed to oxidative agents--reactive oxygen species, for example, singlet oxygen or hydroxyl radicals. Despite this fact, products of oxidation of polyisoprenoids have never been characterized. In this study, chemical oxidation of isoprenoid alcohols (Prenol-2 and -10) was performed using singlet oxygen (generated in the presence of hydrogen peroxide/molybdate or upon photochemical reaction in the presence of porphyrin), oxygen (formed upon hydrogen peroxide dismutation) or hydroxyl radical (generated by the hydrogen peroxide/sonication, UV/titanium dioxide or UV/hydrogen peroxide) systems.

Highly selective inhibition of butyrylcholinesterase by a novel melatonin-tacrine heterodimers.

Novel inhibitors of cholinesterases, especially butyrylcholinesterase (BuChE), were obtained by coupling melatonin-tacrine heterodimers via the carbamate bond. Compounds 14a-i possessed potent cholinesterase inhibitory activity (with IC50 values as low as 1.18 nM for acetylcholinesterase (AChE) and 0.

3-(2-Acetamido-eth-yl)-1H-indol-5-yl 4-nitro-phenyl carbonate.

In the title mol-ecule, C(19)H(17)N(3)O(6), the indole ring system is essentially planar (r.m.s.