Flavaglines Alleviate Doxorubicin Cardiotoxicity: Implication of Hsp27

Background: Despite its effectiveness in the treatment of various cancers, the use of doxorubicin is limited by a potentially fatal cardiomyopathy. Prevention of this cardiotoxicity remains a critical issue in clinical oncology. We hypothesized that flavaglines, a family of natural compounds that display potent neuroprotective effects, may also alleviate doxorubicininduced cardiotoxicity. Methodology/Principal Findings: Our in vitro data established that a pretreatment with flavaglines significantly increased viability of doxorubicin-injured H9c2 cardiomyocytes as demonstrated by annexin V, TUNEL and active caspase-3 assays. We demonstrated also that phosphorylation of the small heat shock protein Hsp27 is involved in the mechanism by which flavaglines display their cardioprotective effect. Furthermore, knocking-down Hsp27 in H9c2 cardiomyocytes completely reversed this cardioprotection. Administration of our lead compound (FL3) to mice attenuated cardiomyocyte apoptosis and cardiac fibrosis, as reflected by a 50 % decrease of mortality. Conclusions/Significance: These results suggest a prophylactic potential of flavaglines to prevent doxorubicin-induce

Synthesis of a calothrixin B isomer with a novel 7H-indolo[2,3-j]phenanthridine-7,13(8H)-dione structure

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Layer‑by‑Layer Assemblies Based on a Cationic β‑Cyclodextrin Polymer: Chiral Stationary Phases for Open‑Tubular Electrochromatography

Non-covalent chiral stationary phases for open-tubular capillary electrochromatography (OT-CEC) were developed using polyelectrolyte multilayer (PEM) coatings. These chiral coatings were made by alternately flushing the separation capillary with cationic and anionic polymers using a polymer of trimethylammonium-β-CD (pCD+) as a chiral selector. The layer-by-layer construction was monitored by EOF measurements. To our knowledge, it is the first OT-CEC chiral stationary phase based on a layer-by-layer assembly including an ionic cyclodextrin polymer. The composition of PEM coating was optimized as regards chiral separation. Thus, the influence of the nature of the first adsorbed cationic polymer (pCD+, polyethyleneimine or poly(diallyldimethyl ammonium chloride)) and the influence of the anionic polymer (poly(sodium 4-styrenesulfonate), polycarboxymethyl-β-CD or chondroitin sulfate) were studied with regard to the apparent surface charge and the enantioselective properties of the coatings. Interactions between the studied enantiomers and the internal layers of the stationary phase were pointed out. We found that the optimal stationary phase was based on a pCD+/poly(sodium 4-styrenesulfonate)/pCD+ three-layer coating. This optimal coating was found to be stable as evidenced by the RSD of 2.2 % for the EOF values calculated from five independent analyses. It was effective for the chiral separation of both neutral and anionic solutes