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Benzofuran–Chalcone Hybrids as Potential Multifunctional Agents against Alzheimer’s Disease: Synthesis and in vivo Studies with Transgenic Caenorhabditis elegans
Author(s) -
Sashidhara Koneni V.,
Modukuri Ram K.,
Jadiya Pooja,
Dodda Ranga Prasad,
Kumar Manoj,
Sridhar Balasubramaniam,
Kumar Vikash,
Haque Rizwanul,
Siddiqi Mohammad Imran,
Nazir Aamir
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402291
Subject(s) - chalcone , caenorhabditis elegans , benzofuran , neurodegeneration , acetylcholinesterase , in vivo , transgene , oxidative stress , genetically modified mouse , biology , pharmacology , biochemistry , microbiology and biotechnology , chemistry , medicine , disease , stereochemistry , genetics , gene , enzyme
In the search for 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 by using a transgenic Caenorhabditis elegans model that expresses the human β‐amyloid (Aβ) peptide. Among the hybrids investigated, ( E )‐3‐(7‐methyl‐2‐(4‐methylbenzoyl)benzofuran‐5‐yl)‐1‐phenylprop‐2‐en‐1‐one ( 4 f ), ( E )‐3‐(2‐benzoyl‐7‐methylbenzofuran‐5‐yl)‐1‐phenylprop‐2‐en‐1‐one ( 4 i ), and ( E )‐3‐(2‐benzoyl‐7‐methylbenzofuran‐5‐yl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one ( 4 m ) significantly decreased Aβ aggregation and increased acetylcholine (ACh) levels along with the overall availability of ACh at the synaptic junction. These compounds were also found to decrease acetylcholinesterase (AChE) levels, reduce oxidative stress in the worms, lower lipid content, and to provide protection against chemically induced cholinergic neurodegeneration. Overall, the multifunctional effects of these hybrids qualify them as potential drug leads for further development in AD therapy.