The mitochondrial effects of two fluoride curcumin derivatives were studied. They induced the collapse of mitochondrial membrane potential (Dw), increased mitochondrial respiration, and decreased O 2 Å À production and promoted Ca 2þ release. These effects were reversed by the recoupling agent 6-Ketocholestanol, but not by cyclosporin A, an inhibitor of the permeability transition pore (PTP), suggesting that these compounds act as uncoupling agents. This idea was reinforced by the analysis of the physico-chemical properties of the compounds indicating, that they are mainly in the anionic form in the mitochondrial membrane. Moreover, they are able to induce PTP opening by promoting the oxidation of thiol groups and the release of cytochrome c, making these two molecules potential candidates for induction of apoptosis.

The ionization and lipophilicity properties of the second-generation catechol-O-methyltransferase (COMT) inhibitors entacapone (1), nitecapone (2), and tolcapone (3) which share the same nitrocatechol structure but have remarkably different pharmacokinetic profiles are investigated to identify relationships between some of these physicochemical parameters and the blood-brain-barrier (BBB) passage. In addition, the lipophilicity behavior of the simpler, structurally related analogues 4 -11 is studied. Combined descriptors such as Dlog P (difference between log P in two different solvent systems) and diff(log P NÀI ) (difference between log P of two different electrical forms of a given solute in the same system) provide insight into inter-and intramolecular interactions characteristic of the analyzed compounds.