Functionalized Dienes: A New Series of Potential Agents for the Treatment of Alzheimer’s Disease

Abstract

We report a series of functionalized dienes as compounds of great potential in the treatment of Alzheimer's disease due to their antioxidant activity and ability to inhibit the enzyme acetylcholinesterase. The dienes tested showed high enzymatic inhibition capacity and accentuated antioxidant activity, which are comparable to or higher than the standards tested. Molecular docking studies were performed to confirm the experimental results. We also describe the correlation values between the antioxidant activity and oxidation potentials. Predicted bioactivity scores and quantum studies were also determined.

In vitro evidence that the anti‐inflammatory effect of synthetic cinnamate‐derived dienes is directly linked to a macrophage repolarization

“…Cinnamate‐derived dienes were readily synthesized from allylic phosphonium salts and aldehydes through the Wittig reaction under mild alkaline conditions, as previously reported by Sá et al [13, 14]. They were purified by simple crystallization with 2‐propanol or, alternatively, by column chromatography on silica gel to give single products as stable crystalline solids with homogeneous melting point.…”

“…They are also structural motifs of spread occurrence in natural products and pharmaceutically relevant compounds [11, 12]. Recently, a series of nitrophenyl‐substituted dienes derived from cinnamates was found to possess pronounced antioxidant activity [13, 14]. Due to the involvement of redox processes in the inflammatory response [15], we envisioned that these electron‐deficient dienes would be interesting candidates as anti‐inflammatory agents In spite of the anti‐inflammatory effect associated with these compounds, including their influence on important inflammatory cytokines, currently there is no scientific evidence involving the effect of these compounds on macrophage polarization.…”

Pyrazolines as potential anti-Alzheimer's agents: DFT, molecular docking, enzyme inhibition and pharmacokinetic studies

“…The enzymatic inhibition was measured using the method described previously. 27 Briefly, 90 μL of 50 mmol L −1 Tris-HCl buffer pH 8.0, 30 μL of a buffer solution containing the compound (0.1 mg mL −1 ) dissolved in MeOH and 15 μL of an AChE solution containing 0.25 U mL −1 , dissolved in 50 mmol L −1 Tris-HCl pH 8 buffer, containing 0.1% of bovine serum albumin were incubated for 15 min. Then, 25 μL of an acetylthiocholine iodide solution (15 mmol in water) and 140 μL of Ellman's reagent (3 mmol L −1 in Tris-HCl pH 8.0 buffer containing 0.1 mol L −1 NaCl and 0.02 mol L −1 MgCl 2 ) were added, and the final mixture was incubated for another 30 min at 28 °C.…”

Kinetically Controlled Stereoselective Access to Branched 1,3-Dienes by Ru-Catalyzed Remote Conjugative Isomerization

“…In addition to being a highly prevalent structural element in numerous natural products and biologically active molecules, conjugated dienes serve as pivotal building blocks in the synthesis of a broad range of compounds, ranging from fine chemicals to functional polymers (Figure A). − Because the inherent reactivity of dienes is influenced by the nature, the number, and the relative position of their substituents, they also constitute a particularly modular and versatile platform for the discovery and development of catalytic synthetic methods that streamline access to more complex polyfunctional small molecules. More specifically, beyond any reactivity consideration, transition-metal-catalyzed functionalization of dienes is typically faced with the difficulty of exerting excellent chemo-, regio-, diastereo-, and enantiocontrol …”