Synthesis, biological evaluation, and computational studies of novel fused six-membered O-containing heterocycles as potential acetylcholinesterase inhibitors

An efficient, borax-catalyzed protocol for the synthesis of novel 4-aryl-substituted-4H-pyran derivatives fused to α-pyrone ring in a one-pot is described. By this achievement, some novel 4-aryl substituted 4H-pyrans fused to the α-pyrone ring as potential acetylcholinesterase inhibitors (AChEIs) with good to excellent yields are obtained from a one-pot three-component reaction between various aryl aldehydes, 4-hydroxy-6-methyl-2H-pyran-2-one and malononitrile. The method is a facile, inexpensive, practical and highly efficient one to obtain target compounds. The chemical structures of all compounds were characterized by FT-IR, FT- 13 CNMR and FT- 1 HNMR, MS spectroscopy and also elemental analyses data. Furthermore, the purity of all novel compounds was checked by HPLC. In addition, both molecular modelling studies and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMETox) prediction nominated all compounds as good acetylcholinesterase inhibitors to the potential treatment of Alzheimer, Parkinson and Autism diseases that among them compound 4f showed the best activity against acetylcholinesterase enzyme

Nano-graphene oxide-supported APTESspermine, as gene delivery system, for transfection of pEGFP-p53 into breast cancer cell lines

Purpose: Genetic diseases can be the result of genetic dysfunctions that happen due to some inhibitory and/or environmental risk factors, which are mostly called mutations. One of the most promising treatments for these diseases is correcting the faulty gene. Gene delivery systems are an important issue in improving the gene therapy efficiency. Therefore, the main purpose of this study was modifying graphene oxide nanoparticles by spermine in order to optimize the gene delivery system. Methods: Graphene oxide/APTES was modified by spermine (GOAS) and characterized by FT-IR, DLS, SEM and AFM techniques. Then pEGFP-p53 was loaded on GOAS, transfected into cells and evaluated by fluorescent microscopy and gene expression techniques. Results: FT-IR data approved the GOAS sheet formation. Ninety percent of the particles were less than 56 nm based on DLS analysis. SEM analysis indicated that the sheets were dispersed with no aggregation. AFM results confirmed the dispersed structures with thickness of 1.25±0.87 nm. STA analysis showed that GOAS started to decompose from 400°C and was very unstable during the heating process. The first weight loss up to 200°C was due to the evaporation of absorbed water, the second one observed in the range of 200�550°C was assigned to the decomposition of labile oxygen-and nitrogen-containing functional groups, and the third one above 550°C was attributed to the removal of oxygen functionalities. In vitro release of DNA demonstrated the efficient activity of the new synthesized system. Ninety percent of the cells were transfected and showed the GFP under fluorescence microscopy, and TP53 gene was expressed 51-fold in BT-20 cells compared to β-actin as the reference gene. Flow cytometry analysis confirmed the apoptosis of the cells rather than necrosis. Conclusion: It could be concluded that the new synthesized structure could transfer a high amount of the therapeutic agent into cells with best activity. © 2020 Mirzaie et al

Ultrasound-assisted and efficient knoevenagel condensation reaction catalyzed by silica sodium carbonate nanoparticles

An efficient and ultrasound-assisted route to the synthesis of arylidene malononitriles/methylciano- or ethylciano acetates in a one-pot reaction catalyzed by silica sodium carbonate nanoparticles (SSC NPs) is described. In this reaction, SSC NPs demonstrated high efficiency as catalyst to obtain target products. By this achievement, a wide range of α,β-unsaturated compounds as Knoevenagel condensation products with good to excellent yields are obtained from reaction between numerous arylaldehydes, and malononitrile, methyl cianoacetate or ethyl cianoacetate. Target products which prepared in high yield and high purity can be candidate as important biologically active molecules. This method is an easy, cheap, rapid and highly efficient for the synthesis of desired products. In addition, capability of catalyst to separate from reaction mixture and reuse in further runs and being compatible with green chemistry are considered as other advantages of this procedure. All products were deduced from their FT-IR and FT-NMR spectroscopic and elemental analysis data. This work is licensed under a Creative Commons Attribution 4.0 International License