Fluorinated benzophenone derivatives: Balanced multipotent agents for Alzheimer's disease

Belluti, Federica; Simone, Angela De; Tarozzi, Andrea; Bartolini, Manuela; Djemil, Alice; Bisi, Alessandra; Gobbi, Silvia; Montanari, Serena; Cavalli, Andrea; Andrisano, Vincenza; Bottegoni, Giovanni; Rampa, Angela

doi:10.1016/j.ejmech.2014.03.042

Cited by 23 publications

(20 citation statements)

References 41 publications

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“…The human neuroblastoma cell line SH-SY5Y was obtained from the European Collection of Cell Cultures (Centre for Applied Microbiology and Research). SH-SY5Y cells were cultured according to a previous report [ 79 ] with minor modifications. The cells were grown in MEM and GlutaMax medium (Gibco) and supplemented with 10% (v/v) fetal bovine serum (Gibco), 100 units/mL penicillin, 100 μg/mL streptomycin (Gibco), and 1% non-essential amino acid solution (Gibco).…”

Section: Methodsmentioning

confidence: 99%

Tetrabromobisphenol A Is an Efficient Stabilizer of the Transthyretin Tetramer

et al. 2016

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Amyloid formation of the human plasma protein transthyretin (TTR) is associated with several human disorders, including familial amyloidotic polyneuropathy (FAP) and senile systemic amyloidosis. Dissociation of TTR’s native tetrameric assembly is the rate-limiting step in the conversion into amyloid, and this feature presents an avenue for intervention because binding of an appropriate ligand to the thyroxin hormone binding sites of TTR stabilizes the native tetrameric assembly and impairs conversion into amyloid. The desired features for an effective TTR stabilizer include high affinity for TTR, high selectivity in the presence of other proteins, no adverse side effects at the effective concentrations, and a long half-life in the body. In this study we show that the commonly used flame retardant tetrabromobisphenol A (TBBPA) efficiently stabilizes the tetrameric structure of TTR. The X-ray crystal structure shows TBBPA binding in the thyroxine binding pocket with bromines occupying two of the three halogen binding sites. Interestingly, TBBPA binds TTR with an extremely high selectivity in human plasma, and the effect is equal to the recently approved drug tafamidis and better than diflunisal, both of which have shown therapeutic effects against FAP. TBBPA consequently present an interesting scaffold for drug design. Its absorption, metabolism, and potential side-effects are discussed.

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Section: Methodsmentioning

confidence: 99%

Tetrabromobisphenol A Is an Efficient Stabilizer of the Transthyretin Tetramer

et al. 2016

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“…This direct aroylation reaction combines PdCl 2 (Ph 3 P) 2 After further investigation with several palladium complexes and bases to find a suitable conditions for aroylation of potassium aryltrifluoroborates under microwave irradiation, the effective catalyst effect of PdCl 2 (Ph 3 P) 2 complex has been observed and successfully synthesize series of fluoro-substituted aromatic ketones in high yields.…”

Section: Resultsmentioning

confidence: 99%

“…Fluoro-substituted aromatic ketones are very active pharmaceutical ingredients useful for pharmaceutical application such as anti-inflammatory effects. Introducing fluorine moiety is demanding methodology in medicinal chemistry to adjust binding affinity of small molecules for biological targets and control metabolic reactivity [1] [2]. Fluorinated benzophenones served as starting point for the synthesis of many small benzophenone analogs.…”

Section: Introductionmentioning

confidence: 99%

Efficient Cross-Coupling Reaction of Aryltrifluoroborates and Aroyl Chlorides for the Synthesis of Fluorine Substituted Aromatic Ketones

Al-Masum¹,

Islam²,

Clopton³

2019

IJOC

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The direct aroylation of ArCOPdCl with potassium aryltrifluoroborates establishes a new cross-coupling synthetic tool for the synthesis of various fluorine substituted benzophenones. The new microwave irradiated process is very efficient and produce high yield benzophenone products within minutes.arylboronic acids [5] [6]. In this work, a new reaction method establishes for the direct aroylation reaction of potassium aryltrifluoroborates and ArCOCl in the presence of PdCl 2 (Ph 3 P) 2 (Scheme 1).

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“…8 Usually, the starting point for the design of such compounds is the structure of a known AChE inhibitor, which is linked to an antioxidant pharmacophoric moiety, [11][12][13][14][15][16][17][18] e.g. phenolics and polyphenolics derived fragments.…”

Section: Introductionmentioning

confidence: 99%