28165-46-0Relevant academic research and scientific papers
A new biological prospective for the 2-phenylbenzofurans as inhibitors of α-glucosidase and of the islet amyloid polypeptide formation
Delogu, Giovanna Lucia,Era, Benedetta,Floris, Sonia,Medda, Rosaria,Sogos, Valeria,Pintus, Francesca,Gatto, Gianluca,Kumar, Amit,Westermark, Gunilla Torstensdotter,Fais, Antonella
, p. 428 - 435 (2020/12/28)
In this study, we have investigated a series of hydroxylated 2-phenylbenzofurans compounds for their inhibitory activity against α-amylase and α-glucosidase activity. Inhibitors of carbohydrate degrading enzymes seem to have an important role as antidiabetic drugs. Diabetes mellitus is a wide-spread metabolic disease characterized by elevated levels of blood glucose. The most common is type 2 diabetes, which can lead to severe complications. Since the aggregates of islet amyloid polypeptide (IAPP) are common in diabetic patients, the effect of compounds to inhibit amyloid fibril formation was also determined. All the compounds assayed showed to be more active against α-glucosidase. Compound 16 showed the lowest IC50 value of the series, and it is found to be 167 times more active than acarbose, the reference compound. The enzymatic activity assays showed that compound 16 acts as a mixed-type inhibitor of α-glucosidase. Furthermore, compound 16 displayed effective inhibition of IAPP aggregation and it manifested no significant cytotoxicity. To predict the binding of compound 16 to IAPP and α-glucosidase protein complexes, molecular docking studies were performed. Altogether, our results support that the 2-phenylbenzofuran derivatives could represent a promising candidate for developing molecules able to modulate multiple targets involved in diabetes mellitus disorder.
Synthesis, molecular docking and cholinesterase inhibitory activity of hydroxylated 2-phenylbenzofuran derivatives
Fais, Antonella,Kumar, Amit,Medda, Rosaria,Pintus, Francesca,Delogu, Francesco,Matos, Maria J.,Era, Benedetta,Delogu, Giovanna L.
, p. 302 - 308 (2018/12/11)
We have designed, synthesized and evaluated a series of hydroxylated 2-phenylbenzofuran derivatives as potential cholinesterase inhibitors. Starting from a series of 2-phenylbenzofurans previously published, in this paper we present a complete synthesis and the influence on the activity of one or two hydroxyl groups located in meta or in meta and para positions respectively of the 2-phenyl ring and highlight the importance of position of hydroxyl groups. Moreover, simultaneous introduction of halogen at position 7 of the benzofuran scaffold resulted in an improved inhibitory activity against the enzyme. To further provide molecular insight and to identify the most probable ligand-binding site of the protein, docking studies were performed for the top-ranked compounds. Docking results revealed conserved ligand-binding residues and supported the role of catalytic site residues in enzyme inhibition.
Lewis Base Catalyzed Intramolecular Reduction of Salicylaldehydes by Pinacol-Derived Chlorohydrosilane
Assoah, Benedicta,Vale, Jo?o R.,Kalenius, Elina,Veiros, Luis F.,Candeias, Nuno R.
supporting information, p. 2910 - 2917 (2018/06/27)
A newly developed stable chlorohydrosilane derived from pinacol is herein described. This was successfully used in the reduction of salicylaldehydes in reasonable to excellent yields (51–97 %). The ability of the hydrosilane to react as a reducing agent is increased upon the in situ formation of a trialkoxyhydrosilane and activation with a Lewis base, as further indicated by density functional theory studies. 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU) was identified to be a suitable catalyst for this metal-free reduction, promoting the regio- and chemoselective reduction of aldehydes in ortho-position to phenols, despite the presence of vicinal ketones. The performance of pinacol-derived chlorohydrosilane in the reduction of salicylaldehydes was further observed to be superior to that of well-established commercially available chlorohydrosilanes.
2-Phenylbenzofuran derivatives as butyrylcholinesterase inhibitors: Synthesis, biological activity and molecular modeling
Delogu, Giovanna L.,Matos, Maria J.,Fanti, Maura,Era, Benedetta,Medda, Rosaria,Pieroni, Enrico,Fais, Antonella,Kumar, Amit,Pintus, Francesca
, p. 2308 - 2313 (2016/04/20)
A series of 2-phenylbenzofurans compounds was designed, synthesized and evaluated as cholinesterase inhibitors. The biological assay experiments showed that most of the compounds displayed a clearly selective inhibition for butyrylcholinesterase (BChE), while a weak or no effect towards acetylcholinesterase (AChE) was detected. Among these benzofuran derivatives, compound 16 exhibited the highest BChE inhibition with an IC50 value of 30.3 μM. This compound was found to be a mixed-type inhibitor as determined by kinetic analysis. Moreover, molecular dynamics simulations revealed that compound 16 binds to both the catalytic anionic site (CAS) and peripheral anionic site (PAS) of BChE and it displayed the best interaction energy value, in agreement with our experimental data.
Asymmetric induction via short-lived chiral enolates with a chiral C-O axis
Yoshimura, Tomoyuki,Tomohara, Keisuke,Kawabata, Takeo
supporting information, p. 7102 - 7105 (2013/06/27)
A novel method has been developed for the asymmetric cyclization of alkyl aryl ethers. The reactions were assumed to proceed via short-lived chiral enolate intermediates with a chiral C-O axis to give cyclic ethers with tetrasubstituted carbon in up to 99% ee. The half-life of racemization of the chiral enolate intermediate was roughly estimated to be ～1 s at -78 C.
Synthesis of ACAT inhibitors through substitution using allylic picolinate and copper reagent
Kobayashi, Yuichi,Lalitnorasate, Paveena,Kaneko, Yuki,Kiyotsuka, Yohei,Endo, Yoshiki
scheme or table, p. 6018 - 6021 (2010/11/21)
Amide of an octanoic acid possessing an aryl group at C3 position is a highly potent ACAT inhibitor. In this paper, we describe a synthetic access to this class of compounds as optically active forms. The key reaction is substitution of the allylic picoli
Second-generation cycloSal-d4TMP pronucleotides bearing esterase-cleavable sites - The "trapping" concept
Meier, Chris,Ducho, Christian,Jessen, Henning,Vukadinovic-Tenter, Dalibor,Balzarini, Jan
, p. 197 - 206 (2007/10/03)
An extension of the cycloSal-pronucleotide approach is presented. Attachment of an enzyme-cleavable ester/acylal group to the cycloSal-d4TMP triesters should allow these compounds to be trapped intracellularly after cleavage. The ester/acylal groups were introduced in the 3- or 5-position of the cycloSal ring system, and surprising differences were observed in hydrolysis studies in CEM cell extracts with respect to the ester/acylal moiety. While acetyl and levulinyl esters were readily cleaved, alkyl esters of cycloSal-d4TMP acids proved to be resistant to enzymatic cleavage. In contrast, AM-, POM- and POC-acylals were rapidly cleaved in the extracts, leading to cycloSal-d4TMP acids. The antiviral activity of the compounds against HIV is also presented. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
Novel cycloSal nucleotides with reduced inhibitory potency toward human butyrylcholinesterase
Ducho,Jessel,Gisch,Balzarini,Meier
, p. 519 - 522 (2008/02/02)
Two novel cycloSal-d4T monophosphates (d4TMPs) with increased stem demand have been synthesized via a new synthetic route. While 3-cyclohexyl-cycloSal d4TMP did not show a significantly reduced inhibitory potency toward human butyrylcholinesterase, the opposite was the case for the second novel pronucleotide, bis-(cycloSal-d4TMP). Copyright Taylor & Francis, Inc.
