Synthesis, kinetic studies and molecular modeling of novel tacrine dimers as cholinesterase inhibitors.

This study presents the synthesis of 15 new tacrine dimers as well as the Ki and IC50 results, studies of the kinetic mechanism, and molecular docking analysis of the dimers in relation to the cholinesterases hAChE, hBChE, EeAChE and eqBChE. In addition to spectroscopic characterization, X-ray structure determination was performed for two of the new compounds. These new dimers were found to be mixed nanomolar inhibitors of the evaluated targets with a broad and significant selectivity profile, and these properties are dependent on both the type of the linker and the volume of the hydroacridine alicyclic ring.

Design of new drugs for the treatment of Alzheimer's disease based on tacrine structure.

Tacrine was the first drug approved by FDA for the treatment of Alzheimer's disease. However, its use was restricted in function of side effects observed in some patients. Investigations on the structural basis by which tacrine inhibits cholinesterases activity brought new perspectives for the design of more potent analogs with fewer side effects.

Nitroprusside-PEO enthalpic interaction as a driving force for partitioning of the [Fe(CN)(5)NO](2-) anion in aqueous two-phase systems formed by poly(ethylene oxide) and sulfate salts.

Ions are known to concentrate in the salt-enriched phase of aqueous two-phase systems, with the only known exception being the pertechnetate anion, TcO(4)(-). We have discovered a second ion, nitroprusside anion (NP), which is markedly transferred from the salt phase to the polymer phase. The partitioning behavior of [Fe(CN)(5)NO](2-) anion was investigated in ATPS formed by poly(ethylene oxide) of molar mass 3350 and 35000 g mol(-1), and different sulfate salts (Na(2)SO(4), Li(2)SO(4), and MgSO(4)).