Benzofuran-Chalcone Hybrids as Potential Multifunctional Agents against Alzheimer’s disease: Synthesis and in vivo Studies Employing Transgenic Caenorhabditis elegans

Abstract

In search of effective multifunctional agents for the treatment of Alzheimer’s disease (AD), a series of novel hybrids incorporating benzofuran and chalcone fragments were designed and synthesized. These hybrids were screened using a transgenic Caenorhabditis elegans (C. elegans) model, which expresses the human amyloid-beta peptide. Among the hybrids investigated, (E)-3-(7-methyl-2-(4-methylbenzoyl)benzofuran-5-yl)-1-phenylprop-2-en-1-one (4f), (E)-3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-phenylprop-2-en-1-one (4i) and (E)-3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one (4m) significantly reduced the aggregation of amyloid-beta peptide (Aβ), and increased the acetylcholine (ACh) levels along with the overall availability of ACh at the synaptic junction. Furthermore, these compounds were also found to decrease acetylcholinesterase (AChE) levels, reduce oxidative stress in the worms, lower lipid content and provided protection against chemically induced cholinergic neurodegeneration. Overall, the multifunctional effects of the new hybrids qualified them as potential drug leads for further development in Alzheimer’s therapy.