Covalent chloramine inhibitors of blood platelet functions: Computational indices for their reactivity and antiplatelet activity

Taurine and Its Derivatives: Analysis of the Inhibitory Effect on Platelet Function and Their Antithrombotic Potential

“…They exhibited an elevated reactive ability (chemoselectivity) with respect to various sulfur-containing groups in amino acids and peptides and proved a firm inhibition of platelet aggregation triggered by ADP or collagen. Their effect on aggregation might be ascribed to the chemoselectivity and modification of the thiol group in P2Y 12 ADP receptor, similar to that elicited by the main covalent inhibitors of platelets, the thienopyridine compounds (clopidogrel, prasugrel) [138]. Furthermore, an in vitro comparison between the antiaggregant effect of the amide analog of taurine chloramine, N-propionyl-N-chlorotaurine (PCT) and the alkyl analog, N-isopropyl-N-chlorotaurine (IPCT) was performed.…”

“…Still far from being elucidated, the potential mechanisms underlying the overall inhibitory influence of taurine and its derivatives on platelet activity can be summarized as follows: decreased platelet TxA 2 [41] and TxB 2 production [113]; suppression of platelet cyclooxygenase activity [144,158]; stimulation of calmodulin-mediated platelet Ca, Mg-ATPase activity [140,162], attenuation of platelet Ca 2+ influx [141,154] and suppression of intraplatelet Ca 2+ response to activating agonists [156]; platelet stabilization against PAF [126,143,156]; suppression of β-TG and ATP release response to agonists, as markers of discharge from alpha and dense platelet granules [154]; preservation of platelet glutathione pool [113]; increased affinity of covalent inhibitors (e.g., DT, PCT, IPCT) to molecular targets, i.e., sulfur-containing groups on platelet surface (such might be the thiol group of P2Y 12 ADP receptor) [135][136][137][138][139]; and pronounced enhancement of hydrogen sulfide (H 2 S) plasma level [163][164][165][166], H 2 S being known to inhibit platelet activation and aggregation [167][168][169][170][171][172]. Taurine may also interfere with platelet activity by generating complementary processes such as an increase of the endothelial NO release [173][174][175][176], decrease of epinephrine and norepinephrine circulant level [177][178][179], suppression of CD147-dependent M...…”