Synthesis, Biological Evaluation, and Molecular Simulation of Chalcones and Aurones as Selective MAO-B Inhibitors.

A series of chalcones and aurones were synthesized and evaluated in vitro as monoamine oxidase inhibitors (MAOi). Our results show that aurones, which had not been previously reported as MAOi, are MAO-B inhibitors. Thus, both families inhibited selectively the B isoform of MAO in the micromolar range, offering novel scaffolds for the design of new and potent MAO inhibitors. The main structural requirements for their activity were characterized with the aid of 3D-QSAR and docking studies.

Solvent and temperature effects on the conformational equilibria of a dihydrobenzo[h]quinolinium fluoroborate.

Spectra of the N-phenyl-5,6-dihydro-2,4-diphenylbenzo[h]quinolinium tetrafluoroborate (1) and of the N-phenyl-5,6,8,9-tetrahydro-7-phenyldibenzo[c,h]acridinium tetrafluoroborate (2) were recorded in various solvents and temperatures. The analysis of the (1)H-NMR spectra of the tetrafluoroborate salt 1, recorded in acetone, acetonitrile, 1,1,2,2-tetrachloroethane and chloroform, revealed the existence of an equilibrium between two conformers in solution. Tight ion-pairing in chloroform led to a smaller barrier for interconversion between the two conformers. In more polar solvents, where the dihydrobenzoquinolinium exists as a free cation, theoretical calculations predicted larger barriers. The spectra of 1 in 1,1,2,2-tetrachloroethane also varied with temperature, resembling at higher temperatures the spectrum in CDCl(3) and at 300K spectra in more polar media. Spectra of 2 did not vary with the solvent or the temperature, in an indication of a much higher barrier to conformational interconversion, because of a greater steric hindrance between the N-phenyl substituent and the dihydrobenzo rings.