ABSTRACT
Polyphenols, such as rosmarinic acid, are widely distributed natural products with relevant antioxidant activity. Oxidative stress plays an important role in the pathogenesis of a number of disorders. Here, we report on the synthesis and biological effects of the polyphenolic esters hydroxytyrosyl gallate (1), hydroxytyrosyl protocatechuate (2) and hydroxytyrosyl caffeate (3), structurally related to rosmarinic acid. The three compounds showed a greater free radical scavenging activity than their precursors and also than rosmarinic acid. Esters 1 and 3 significantly reduced thrombin-evoked platelet aggregation, which is likely mediated to the attenuation of thrombin-stimulated Ca(2+) release and entry. The three compounds reduced the ability of platelets to accumulate Ca(2+) in the intracellular stores, probably by enhancing the Ca(2+) leakage rate and reduced store-operated Ca(2+) entry in these cells. These observations suggest that the structurally-simplified analogs to rosmarinic acid, compounds 1 and 3, might be the base of therapeutic strategies to prevent thrombotic complications associated to platelet hyperaggregability due to oxidative stress.
Subject(s)
Antioxidants/chemical synthesis , Blood Platelets/drug effects , Caffeic Acids/chemical synthesis , Cinnamates/chemistry , Depsides/chemistry , Gallic Acid/analogs & derivatives , Platelet Aggregation Inhibitors/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Blood Platelets/metabolism , Caffeic Acids/chemistry , Caffeic Acids/pharmacology , Calcium/metabolism , Gallic Acid/chemical synthesis , Gallic Acid/chemistry , Gallic Acid/pharmacology , Humans , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Thrombin/metabolism , Rosmarinic AcidABSTRACT
Five new bulky moiety-modified analogues of the sandalwood odorant Polysantol have been synthesized by aldol condensation of appropriate aldehydes with butanone, deconjugative alpha-methylation of the resulting alpha,beta-unsaturated ketones, and reduction of the corresponding beta,gamma-unsaturated ketones. The final compounds were evaluated organoleptically and one of them seemed to be of special interest for its natural sandalwood scent.
