Bis -chalcones obtained via one-pot synthesis as the anti-neurodegenerative agents and their effect on the HT-22 cell line.

Autor:	Olender D; Chair and Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806, Poznań, Poland., Kujawski J; Chair and Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806, Poznań, Poland., Skóra B; Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszów, Poland., Baranowska-Wójcik E; Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna 8, 20-704, Lublin, Poland., Sowa-Kasprzak K; Chair and Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806, Poznań, Poland., Pawełczyk A; Chair and Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806, Poznań, Poland., Zaprutko L; Chair and Department of Organic Chemistry, Faculty of Pharmacy, Poznan University of Medical Sciences, Rokietnicka 3, 60-806, Poznań, Poland., Szwajgier D; Department of Biotechnology, Microbiology and Human Nutrition, University of Life Sciences in Lublin, Skromna 8, 20-704, Lublin, Poland., Szychowski KA; Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszów, Poland.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Aug 30; Vol. 10 (17), pp. e37147. Date of Electronic Publication: 2024 Aug 30 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e37147
Abstrakt:	In the area of research on neurodegenerative diseases, the current challenge is to search for appropriate research methods that would detect these diseases at the earliest possible stage, but also new active structures that would reduce the rate of the disease progression and minimize the intensity of their symptoms experienced by the patient. The chalcones are considered in the context of candidates for new drugs dedicated to the fight against neurodegenerative diseases. The synthesis of bis -chalcone derivatives (3a-3d), as aim molecules was performed. Their structures were established by applying 1 H NMR, 13 C NMR, MS, FT-IR and UV-Vis spectra. All bis -chalcones were synthesized from terephthalaldehyde and appropriate aromatic ketone as substrates in the Claisen-Schmidt condensation method and evaluated in the biological tests and in silico analysis. Compounds exerted antioxidant activity using the HORAC method ( 3a-3d ) and decreased the activities of GPx, COX-2 ( 3b-3d ) , GR ( 3a-3c ) and CAT ( 3a,3b) . The high anti-neurodegenerative potential of all four bis- chalcones was observed by inhibition of acetyl- (AChE) and butyrylcholinesterase (BChE) and a positive effect on the mouse hippocampal neuronal HT-22 cell line (LDH release and PGC-1α, PPARγ and GAPDH protein expression). TD-DFT method (computing a number of descriptors associated with HOMO-LUMO electron transition: electronegativity, chemical hardness and potential, first ionization potential, electron affinity) was employed to study the spectroscopic properties. This method showed that the first excited state of compounds was consistent with their maximum absorption in the computed UV-Vis spectra, which showed good agreement with the experimental spectrum using PBE1PBE functional. Using in silico approach, interactions of bis -chalcones with selected targets (aryl hydrocarbon receptor (AhR) PAS-A Domain, ligand binding domain of human PPAR-γ, soman-aged human BChE-butyrylthiocholine complex, Torpedo californica AChE:N-piperidinopropyl-galanthamine complex and the COX-2-celecoxib complex) were characterized. Results obtained in in silico models were consistent with in vitro experiments. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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