title: Benzofuran-chalcone hybrids as potential multifunctional agents against Alzheimer's disease: synthesis and in vivo studies with transgenic Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Jankipuram Extension, Sitapur Road, Lucknow 226031 (India). kv_sashidhara@cdri.res.in.
authors.forename: Koneni V
authors.initials: KV
authors.lastname: Sashidhara
authors.forename: Ram K
authors.initials: RK
authors.lastname: Modukuri
authors.forename: Pooja
authors.initials: P
authors.lastname: Jadiya
authors.forename: Ranga Prasad
authors.initials: RP
authors.lastname: Dodda
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Balasubramaniam
authors.initials: B
authors.lastname: Sridhar
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.forename: Rizwanul
authors.initials: R
authors.lastname: Haque
authors.forename: Mohammad Imran
authors.initials: MI
authors.lastname: Siddiqi
authors.forename: Aamir
authors.initials: A
authors.lastname: Nazir
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D000975:Antioxidants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001572:Benzofurans / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000378:metabolism; D002599:Chalcone / Q000737:chemistry*; D047188:Chalcones / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D006801:Humans; D008856:Microscopy, Fluorescence; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D018384:Oxidative Stress / Q000187:drug effects; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C000599661:3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-(thiophen-2-yl)prop-2-en-1-one; C000599660:3-(2-benzoyl-7-methylbenzofuran-5-yl)-1-phenylprop-2-en-1-one; C000599659:3-(7-methyl-2-(4-methylbenzoyl)benzofuran-5-yl)-1-phenylprop-2-en-1-one; D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001572:Benzofurans; D047188:Chalcones; D013876:Thiophenes; D002599:Chalcone; D000110:Acetylcholinesterase; C105430:benzofuran; D000109:Acetylcholine
keywords: Alzheimer’s disease; Caenorhabditis elegans; benzofurans; beta-amyloid; chalcones