The Use of Triphenyl Phosphonium Cation Enhances the Mitochondrial Antiplatelet Effect of the Compound Magnolol

Abstract

Although platelets are anucleated cells, they have fully functional mitochondria, and currently, it is known that several processes that occur in the platelet require the action of mitochondria. There are plenty of mitochondrial-targeted compounds described in the literature related to cancer, however, only a small number of studies have approached their interaction with platelet mitochondria and/or their effects on platelet activity. Recent studies have shown that magnolia extract and mitochondria-targeted magnolol can inhibit mitochondrial respiration and cell proliferation in melanoma and oral cancer cells, respectively, and they can also induce ROS and mitophagy. In this study, the effect of triphenylphosphonium cation, linked by alkyl chains of different lengths, to the organic compound magnolol on human-washed platelets was evaluated. We demonstrated that the addition of triphenylphosphonium by a four-carbon linker to magnolol (MGN4) considerably enhanced the Magnolol antiplatelet effect by a 3-fold decrease in the IC50. Additionally, platelets exposed to MGN4 5 µM showed several differences from the control including increased basal respiration, collagen-induced respiration, ATP-independent respiration, and reduced ATP-dependent respiration and non-mitochondrial respiration.

Linking triphenylphosphonium cation to a bicyclic hydroquinone improves their antiplatelet effect via the regulation of mitochondrial function

“…After reserving the PRP, the tubes were centrifuged again at 900 g for 10 min to obtain platelet-poor plasma (PPP). For the aggregation reaction, PRP was adjusted to 200-250 × 10 6 platelets/mL with PPP [ [63] , [64] , [65] ]. Platelet counting was performed in a counter (Mindray BC-3000 Plus hematology counter, Japan).…”

Novel Mitochondria-Targeted Amphiphilic Aminophosphonium Salts and Lipids Nanoparticles: Synthesis, Antitumor Activity and Toxicity

“…In TPP-conjugates, the combination of a therapeutic or diagnostic load with a phosphonic group is carried out, as a rule, by means of a covalent bond through a linker, the nature of which is given great attention. Thus, data on the influence of the linker nature were presented in many works [34][35][36][37][38][39][40][41]. There is a report on the effect of the R substituent in R-P + Ph 3 salts on their biological properties [42].…”

“…Principal crystallographic parameters of compound 6a based on X-ray diffraction data. ; calcd for C 20 H 47 N 3 P + 360 35…”