Baris Anil

Synthesis of donepezil-based multifunctional agents for the treatment of Alzheimer's disease.

Amyloid beta (Aβ) and cholinesterase enzymes (AChE, BuChE) are important biological targets for the effective treatment of Alzheimers disease. In this study, the aim was to synthesize new donepezil-like secondary amide compounds that display a potent inhibition of cholinesterases and Aβ with antioxidant and metal chelation abilities. All test compounds showed activities against both ChEs and β1-42 inhibition. The most encouraging compound, 20, is an AChE inhibitor with high anti-aggregation activity (55.3%). Based on the results, compound 20 may be a promising structure in further research for new anti-Alzheimers agents.

Design, synthesis and biological activity of 1H-indene-2-carboxamides as multi-targeted anti-Alzheimer agents

Abstract The aim of this study was to design new molecules and evaluate their anticholinesterase and amyloid beta (Aβ1–42) inhibition activities as multifunctional drug candidates for the treatment of Alzheimer’s disease (AD). A series of 5,6-dimethoxy-1H-indene-2-carboxamides (1–22) was synthesized; cholinesterase inhibitory activities of the compounds were measured according to Ellman’s colorimetric assay, while the thioflavin T assay was used for measuring the inhibition of Aβ1–42 aggregation. The results revealed that most compounds showed higher inhibitory activity against BuChE than AChE. Compounds 20 and 21 were found to be the most potent BuChE inhibitors with respective IC50 values of 1.08 and 1.09 μM. Compounds 16, 20, 21 and 22 exhibited remarkable inhibition of Aβ1–42 aggregation. Kinetic analysis showed that the most potent BuChE inhibitor (20) acted as a noncompetitive inhibitor. Docking studies suggested that inhibitor 20 displayed many potential hydrogen-bondings with the PAS of BuChE. These results suggest that compound 20 may be an especially promising multifunctional drug for the prevention and treatment of AD.

Synthesis and Characterization of Novel Aryl Cyclitols: Polycyclitols

Abstract New polycyclitols were synthesized starting from 1,4-naphthoquinone. An endo-selective Diels–Alder cycloaddition between 1,4-naphthoquinone and 1-acetoxybutadiene afforded a diketone. Reduction of the diketone with a NaBH4-CeCl3 · 7H2O system gave a new cyclitol analog diol acetate. Acetylation of this compound afforded a triacetate. Oxidation of the double bond of the triacetate compound with OsO4 followed by acetylation of hydroxyl groups gave the pentaacetate, whose structure was established unequivocally via application of x-ray crystallographic methods. Hydrolysis of ester groups of pentaacetate under basic condutions furnished the desired and another novel aryl cyclitol. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource: Full experimental and spectral details.] GRAPHICAL ABSTRACT

Preparation, anticholinesterase activity, and docking study of new 2-butenediamide and oxalamide derivatives

Abstract Several new oxalamide and 2-butenediamide derivatives have been designed, synthesized and evaluated as the acetyl- and butyryl-cholinesterase inhibitors for Alzheimer’s disease. The enzyme inhibitory activity of the synthesized compounds was measured using Ellman’s colorimetric method. It was revealed that compound 1a (N,N′-bis-(4-chloro-benzyl)-N,N′-diphenyl-oxalamide) showed maximum activity against BuChE with a half maximal inhibitory concentration (IC50) = 1.86 µM and compound 2a (but-2-enedioic acid bis-[(4-chloro-benzyl)-phenyl-amide]) exhibited optimum AChE (IC50 = 1.51 µM) inhibition with a high-selectivity index. To better understand the enzyme–inhibitor interaction of the most active compounds towards cholinesterase, molecular modelling studies were carried out. Docking simulations revealed that inhibitors 1a and 2a targeted both the catalytic active site and the peripheral anionic site of 1ACJ and 1P0I.

Microwave-Assisted Synthesis, Molecular Docking, and Cholinesterase Inhibitory Activities of New Ethanediamide and 2-Butenediamide Analogues

A novel series of meta-substituted ethanediamide and 2-butenediamide derivatives were synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (AChE) and equine serum butyrylcholinesterase (BuChE). The synthesized compounds were evaluated against ChE enzymes using the colorimetric method described by Ellman et al. (Biochem. Pharmacol., 7, 1961). It was revealed that some synthesized compounds exhibited high anticholinesterase activity, among which compounds 1f and 2f were the most active inhibitors against BuChE (IC50 value=1.47 µM) and AChE (IC50 value=2.09 µM), respectively. Docking simulations revealed that the inhibitors 1f and 2f are capable of simultaneously binding the peripheral anionic site as well as the catalytic anionic site of both ChE enzymes. These derivatives are considered interesting candidates for Alzheimers disease treatment.

One-Pot Synthesis of Mannich Bases Under Solvent-Free Conditions

Abstract A mild and practically convenient one-pot procedure for the Mannich reaction via condensation of amines, aldehydes and malonates, β-ketoesters, or β-dicarbonyl compounds has been carried out without using any organic solvent, metallic catalyst, or Lewis acids or bases at room temperature. The present protocol offers several advantages, such as goods yields, simple procedure with easy workup, and the absence of any volatile, hazardous organic solvents and metallic catalyst. GRAPHICAL ABSTRACT

Synthesis and characterisation of 2,3a,5,6,7a-pentaacetoxy-octahydro-1H-indene from indan-2-ol

A synthesis of 2,3a,5,6,7a-pentaacetoxyoctahydro-1H-indene has been achieved starting from indan-2-ol. The Birch reduction of indan-2-ol gave 4,7-dihydro-2-indanol in high yield which when followed by acetylation, resulted in the corresponding acetates. The OsO4 oxidation of the 2-acetoxy-4,7-dihydroindane followed by acetylation furnished the desired pentaacetates in high yield.

Synthesis and characterisation of 2,3,4a,6,8a-penta-acetoxy decahydronaphthalene from 1,2,3,4-tetrahydronaphthalen-2-ol

2,3,4a,6,8a-Penta-acetoxy decahydronaphthalene has been synthesised starting from 1,2,3,4-tetrahydronaphthalen-2-ol. The Birch reduction of 1,2,3,4-tetrahydronaphthalen-2-ol gave a high yield of 1,2,3,4,5,8-hexahydronaphthalen-2-ol which was acetylated. The OsO4 oxidation of the 1,2,3,4,5,8-hexahydronaphthalen-2-yl acetate followed by further acetylation gave the pentaacetates.

Synthesis and spectral investigation of some new hetaryl-substituted hydroquinolinone derivatives

In recent years, very intensive studies for the synthesizing of heterocyclic compounds have been done because of their important roles as the scaffolds of bioactive substances. Quinoline and its hydro-derivatives are themost popular N-heteroaromatics incorporated into the structures of many pharmaceuticals. It is known that many of hydroquinolinone compounds exhibit a wide spectrum of pharmacological activities, such as antibacterial, antihypertensive, neuroleptic, antipyretic, analgesic, antiphlogistic, antiplasmodial, intrinsic, cytotoxic, antiproliferative, antimalarial and anticancer activities. Furthermore, these compounds are important precursors in the synthesis of natural products such as alkaloids, azastereoids and toxins. The solvent-free reaction has attracted great attention in recent years and proved to have many advantages: reduced pollution, low costs and simplicity in process and handling. In the solid state or in the melt, Knoevenagel condensations and Michael additions have performed very well lately. In this paper, we describe the synthesis, spectroscopic characterization and single crystal x-ray studies of 2-amino-1-aryl-7, 7-dimethyl-4-hetaryl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3carbonitriles 3a–e (Scheme 1). According to our knowledge, this is the first experiment that the Michael additions of enaminones occur by using no catalyst under solvent-free conditions.

Synthesis, characterization, and crystal structure of 6,7a-dichloro-3a-hydroxyoctahydro-1H-indene-2,5-diyl diacetates

The first syntheses and characterizations of 6,7a-dichloro-3a-hydroxyoctahydro-1H-indene-2,5-diyl diacetates were successfully obtained starting from indan-2-ol. Epoxidation of 2 was carried out using mCPBA in methylene chloride followed by acetylation using acetyl chloride to furnish the diacetates. The structures of all synthesized compounds were characterized by spectroscopic methods.