Antiatherogenic Effect of Bisvanillyl-Hydralazone, a New Hydralazine Derivative with Antioxidant, Carbonyl Scavenger, and Antiapoptotic Properties

Abstract

Reactive oxygen species (ROS) generated within the vascular wall trigger low-density lipoprotein (LDL) oxidation, lipid peroxidation, and carbonyl stress that are involved in atherogenesis. We recently reported that the antihypertensive drug, hydralazine, exhibits carbonyl scavenger and antiatherogenic properties, but only moderate antioxidant activity, so that high concentrations are required for inhibiting LDL oxidation. We aimed to develop agents sharing both antioxidant and carbonyl scavenger properties. We have synthesized a new hydralazine derivative, the bisvanillyl-hydralazone (BVH). BVH strongly inhibited LDL oxidation induced by copper and by human endothelial cells (HMEC-1), and prevented the formation of macrophagic foam cells. BVH reduced both the extracellular generation of ROS (superoxide anion and hydrogen peroxide) induced by oxidized LDL (oxLDL), as well as intracellular oxidative stress and proteasome activation, NFkappaB activation, and oxLDL-mediated proinflammatory signaling. In parallel, BVH prevented the carbonyl stress induced by oxLDL on cellular proteins, and blocked the apoptotic cascade as assessed by the inhibition of Bid cleavage, cytochrome C release, and DEVDase activation. Lastly, BVH prevented atherogenesis and carbonyl stress in apoE(-/-) mice. In conclusion, BVH is the prototype of a new class of antioxidant and carbonyl scavenger agents designed for new therapeutical approaches in atherosclerosis.

5,5′-Bis-vanillin derivatives as discriminating sensors for trivalent cations

“…However, the simplicity of the synthetic procedures in addition to the low cost of its preparation 8,9 makes these types of compounds appropriate candidates to evaluate their behaviour as chemosensors for different cations. So we here report the synthesis and evaluation of a library of 5,5 0 -bis-vanillin (1) derivatives (Chart 1) that are cheaply and easily prepared in one step 10 …”

4‐Hydroxynonenal Contributes to Angiogenesis through a Redox‐Dependent Sphingolipid Pathway: Prevention by Hydralazine Derivatives

“…Its antiatherogenic effect has been evaluated in several hypercholesterolemic mice models [43–46]. We recently synthesized a new hydralazine derivative, the bisvanillyl-hydralazone (BVH) (Figure 5(a)), which associates antioxidant (bisvanillin) and carbonyl scavenger (hydralazine) activities and prevents both the carbonyl stress and fatty streaks formation in apoE−/− mice [39]. This led us to evaluate whether these carbonyl scavengers may prevent the angiogenic response triggered by 4-HNE in our experimental model system.…”

“…Cell culture reagents and other materials were from WWR or Sigma. Bisvanillin (BV) and bisvanillyl-hydralazone (BVH) were synthesized as reported [39]. …”

Synthesis, Molecular Structure and Anti-Onchocercal Studies of 1-(Phthalazin-1(2H)-one)[(Pyridin-2-yl)ethylidene]hydrazone

“…Schiff bases of hydralazine (hydrazones) have shown important medicinal properties including antifungal activities [1] [2], antimicrobial properties [3], antihypertensive agents [4], carbonyl scavenger and antiapoptotic activities [5], luminescence properties [6]. Hydrazones have been reported to be less toxic than hydrazines from which they are derived since the-NH 2 group is blocked [7] [8].…”