title: Simple chalcones and bis-chalcones ethers as possible pleiotropic agents.
abstract: The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen-Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity is experimentally determined by reversed-phase thin-layer chromatography method. Most of them are potent in vitro inhibitors of lipid peroxidation and of LOX. Compounds b2 and b3 were found to be the most potent LOX and AChE inhibitors among the tested derivatives with a significant anti-lipid peroxidation profile. The results led us to propose these enone derivatives as new multifunctional compounds against Alzheimer's disease. The results are discussed in terms of structural and physicochemical characteristics of the compounds. Moreover, the pharmacokinetic profile of these compounds was investigated using computational methods.
authors: a Department of Pharmaceutical Chemistry , School of Pharmacy, Aristotle University of Thessaloniki , Thessaloniki , Greece .
authors: Thalia
authors: T
authors: Liargkova
authors: a Department of Pharmaceutical Chemistry , School of Pharmacy, Aristotle University of Thessaloniki , Thessaloniki , Greece .
authors: Dimitra J
authors: DJ
authors: Hadjipavlou-Litina
authors: b Chemistry Department, University of Athens , Panepistimiopolis-Zografou , Greece , and.
authors: Caterina
authors: C
authors: Koukoulitsa
authors: c Department of Pharmaceutical Technology and Pharmaceutical Analysis , School of Pharmacy, University of Patras , Rio Patras , Greece.
authors: Efstathia
authors: E
authors: Voulgari
authors: c Department of Pharmaceutical Technology and Pharmaceutical Analysis , School of Pharmacy, University of Patras , Rio Patras , Greece.
authors: Constantinos
authors: C
authors: Avgoustakis
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D002460:Cell Line; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D019363:Cytochrome P-450 CYP1A1 / Q000737:chemistry / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000737:chemistry / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000737:chemistry / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D047188:Chalcones; D002800:Cholinesterase Inhibitors; D016859:Lipoxygenase Inhibitors; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D005978:Glutathione
keywords: Acetylcholinesterase inhibitors; bis-chalcones; chalcones; lipoxygenase inhibitors; multitarget agents