Organic Chemistry Research
Volume:7 Issue: 2, Summer 2021

The potential of 39 antiviral flavonoids for inhibition of the main protease of coronavirus disease 2019 (COVID-19) was investigated using a molecular docking approach. The studied flavonoids were protease inhibitors of human immunodeficiency viruses (HIV), severe acute respiratory syndrome (SARS), hepatitis C virus (HCV), or Ebola virus. Both affinity and similarity-based molecular docking approach was applied to improve the reliability of the proposition. The estimated binding energy proposed six flavonoids for COVID-19 therapy. Then the similarity-based molecular docking arranged the candidate flavonoids respectively as Quercetin 3-O-(2¢¢-galloyl)-R-Larabinopyranoside from Acer okamotoanum, Tomentin D and Tomentin A from Paulownia tomentosa, Corylifol A and psoralidin from Psoralea and Ladanein from Lamiaceae. The values of similarity score for these phytochemicals respectively were-340, -225, -221, -213, -176, and -152 while the estimated binding energy were -9.52, -7.74, -7.67, -8.09, -8.58, and -8.02 (kcal mol-1). Also, ligand map probing of native and six flavonoids was shown Phe 140, Gly 143, His 164, Glu 166, Gln 189, Thr 190, Thr 26, Cys 145, and Asn 142 amino acids of the active site of main protease of Covid-19 commonly was in the hydrogen or steric interactions with these inhibitors. This study outstanding the inhibitor effect of some antiviral non-nutrient plant compounds against the main protease of COVID-19.

ZnO Nanoparticles were simply synthesized by green biosynthesis method using ficus carica leaf extract. The structure of these nanoparticles was assigned using Fourier transform infrared spectroscopy (IR), Field emission-scanning electron microscopy (FE-SEM) and X‐ray powder diffraction (XRD). The catalytic activity of these nanoparticles was studied for synthesis of 4H-pyrans. A series of 4H-pyrans 3(a-l) were synthesized in good to high yields by reaction of corresponding α,α′-bis(substituted benzylidene) cycloalkanones and malononitrile in the presence of ZnO nanoparticles as a catalyst at 110 ℃. This environmentally friendly method has some advantages such as high efficiency, use of available catalyst, solvent-free reaction conditions and easy operation. The antibacterial activity of synthesized 4H-pyrans was also tested using Staphylococcus aureus and Escherichia coli bacterial strain.

In this research, a high efficient, simply and rapid method was applied for the synthesis of dihydropyrano[3,2-c]chromene derivatives by one-pot, three-component condensation of aldehydes, malononitrile and 4-hydroxycoumarin in H2O/ethanol (1:1 v/v) under reflux conditions. This reaction was run by using nano-silica supported 1,5-Diazabicyclo(4.3.0)non-5-en (DBN) which has been abbreviated as nano-SiO2/DBN under aqueous condition. The nano-SiO2/DBN catalyst was synthesized by reaction between silica chloride and DBN. The main advantages of this procedure are high yields, short reaction times and easy work-up. Furthermore, the catalyst could be reused for five times.

Butyrylcholinesterase (BChE) is considered a promising drug target which plays an essential part in the progression of the late stage of Alzheimer’s disease (AD). Selective BChE inhibitors could be capable drug candidates for a neurodegenerative disorder. So that, a set of novels 1,3,4-thiadiazole derivatives (1c-17c) were designed and synthesized in order to selective inhibitory of BChE. Physicochemical and spectroscopic approaches proved the structures of the synthesized compounds, and the purity of the compounds was confirmed by CHN analysis. The compound’s interactions with amino acid residues in the active sites of acetylcholinesterase (AChE) and BChE were examined by in silico molecular docking studies. In vitro cytotoxicity effects measured by MTT method. For evaluating synthetic substances’ inhibitory activity, Ullman's method was used by AChE from electric eel and BuChE from equine serum. Based on the in vitro inhibitory assay results, compounds 1c (IC50 = 18.34 μM) and 3c (IC50 = 10.45 μM) exhibited inhibitory potency on BChE. Results indicate that these compounds (1c and 3c) possibly will be subjected to further investigations. The present study may be hoped to stimulate efforts to develop of novel BChE inhibitor agents.

Sulfonated ethylenediamine supported on silica-coated magnetite nanoparticles, Fe3O4@SiO2@(CH2)3-en-SO3H/H2SO4 as a new efficient solid acid catalyst was synthesized and fully characterized using various techniques such as FT-IR, FESEM, EDS, TEM, TGA, XRD and VSM. The resulting nanostructure catalyst was applied in the green synthesis of benzimidazole derivatives by the cyclocondensation reaction of o-phenylendiamine with aromatic aldehydes in refluxed ethanol and under solvent-free conditions. The nanocatalyst can be recovered magnetically and can be reused several times without a considerable loss in its catalytic activity.

A novel and practical method for the synthesis of pyridopyrimidine-indole hybrids, using a three-component reaction of thiouracil or 6-amino-N,N-dimethyluracil, various aryl aldehydes and 3-cyanoacetyl indole in the presence of a green heterogeneous nano-catalyst γ-Fe2O3@HAp@PBABMD@Cu was developed. This protocol furnished the desired products in high yields (82-95%) and lower reaction times (18-40 min).

Multiple linear regression (MLR) as modeling tool and Imperialist Competitive Algorithm (ICA) as optimization techniques employed to choose the best set of descriptors and The CORAL software has been used as a tool for linear prediction of -log( IC50) (empirical negative logarithm of half of maximal inhibitory concentration) for Bortezomib derivatives. A high predictive ability was observed for the MLR-ICA model with the best number of empires/ imperialists (nEmp) 90 with root-mean-sum-square errors (RMSE) of 0.0121 and correlation coefficient (R2predict) of 0.9896 in gas phase.
The 25 data sets were randomly splitted into the training set, the calibration set, the test set in the Monte Carlo method and the number of compounds in the each set (n), correlation coefficient (R2) , cross-validated correlation coefficient (Q2), standard error(s) were calculated 13, 0.9826, 0.9780, 0.161 in training set; and n=6, R2= 0.8463 , Q2=0.7377, s=0.715 in test set in the Threshold (T) of 2 and probe of 3, respectively.
From the MLR-ICA method, it was revealed that Espm15u, R5p+, B06 [O-O], F03[N-N], F07[C-O], MATs3m, RDF125v are the most important descriptors. From Monte Carlo simulations, it was found that the presence of double bond and ring, absence of halogens are the most important molecular features affecting the biological activity of the drug.
It was concluded that simultaneous utilization of MLR-ICA and Monte Carlo method can lead to a more comprehensive understanding of the relation between physico-chemical, structural or theoretical molecular descriptors of drugs to their biological activities and facilitate designing of new drugs.

This research presents quantitative structure-activity relationship (QSAR) of half maximal inhibitory concentration (IC50 ) values of 31 different Methotrxate derivatives by employing Multiple linear regression (MLR) and artificial neural networks (ANN), simulated annealing algorithm (SA) and genetic algorithm(GA). Furthermore, CORAL software was used for multiple probability simulation of the studied derivatives. The obtained results from MLR-MLR, MLR-SA, SA-ANN, MLR-GA and GA-ANN approaches were compared and GA-ANN combination showed the best performance according to its correlation coefficient (R2) and mean sum square errors (RMSE). From Monte Carlo simulations, it was found that the presence of double bond, the presence of nitrogen and oxygen, the absence of sulphur and phosphorus and connected sp2 carbon to the ring, are the most important molecular features that affect the biological activity of the drug. It was concluded that the simultaneous application of GA-ANN and Monte Carlo methods can provide a more comprehensive understanding of the relationship between a drug's physicochemical, structural, or theoretical molecular descriptors and its biological activity, leading to accelerate the development of new drugs.

Due to the growing need of the scientific community for targeted drug delivery for specific diseases, the use of which has many side effects for the patient, many studies have been done. In order to better understand and optimize the laboratory process to evaluate the drug delivery ability of drug carriers, the application of theoretical and computational methods plays an important role. Nanocarriers improve drug performance and reduce side effects by altering the pharmacokinetic properties of the drug. In this study, the role of a carbon nanotube as a drug carrier of melphalan, a drug used to treat cancer, was studied using quantum calculations based on density functional theory at the B3LYP level and the 6-311 G base set. To observe the effects of carbon nanotubes on the nature of the drug, the melphalan molecule was attached to the carbon atoms of the carbon nanotube wall surface through its most chemically active sites. Using density functional theory calculations, the adsorption behavior and electronic sensitivity of a carbon nanotube were investigated for melphalan drugs. The drug tends to adsorb on the nanotube via its O atom with adsorption energies of about -94.84 kJ/mol. In the present work, using the quantum mechanical method of density functional theory and using the base set B3LYP/6-311+G(d,p), chemical reactivity properties and adsorption of isocarboxazid on the surface of fullerene C60 molecule (ih) as carriers of the antidepressant drugs were calculated in the gas phase.

In this investigation, an efficient nanomagnetic heterogeneous catalyst, Fe3O4@SiO2@ (CH2)3-en-SO3H/H2SO4 for the synthesis of 2-arylbenzoxazoles by the cyclocondensation reaction of aromatic aldehydes with 2-aminophenol under solvent-free conditions. Catalyst of Fe3O4@SiO2@ (CH2)3-en-SO3H/H2SO4, was synthesized by the immobilization of sulfonated ethylenediamine on the silica-supported magnetic nanoparticles. The catalyst can be recycled magnetically and can be reused several times without a significant decrease in the activity of the catalyst. The present method has several advantages such as excellent efficiency, convenient purification, mild reaction conditions, easy operation and short reaction time. Also nanomagnetic heterogeneous catalyst is found to be an economical, and reusable catalyst with low catalytic loading, a suitable catalyst, stable in air and humidity, heterogeneous and green catalytic.

A series of novel 1,2,3-triazoles-linked indole derivatives were prepared by the reaction of 2-aryl-1-(prop-2-ynyl)-1H-indole-3-carbaldehydes with aryl azides via copper-catalyzed azide-alkyne cycloaddition reactions in the presence of sodium ascorbate, as a reducing agent. The effects of catalysts, solvents, and reaction temperature were investigated. Under the optimal condition, 1,2,3-triazoles linked-indoles were obtained in 63–92% yields.

This study describes a facile and environmentally friendly protocol for the synthesis of highly functionalized tetrahydropyridines via pseudo-five-component reaction of aromatic aldehydes, various amines and ethyl acetoacetate using GA-OPO3H2 as a metal free and natural-based catalyst. In addition to the easy preparation of GA-OPO3H2 from bio-renewable materials, this catalyst can also be recycled and reused without obvious loss of catalytic activity. The synthesis of tetrahydropyridines via this new green methodology offers significant advantages in terms of no use of a solvent, no hazardous waste, uncomplicated work-up and high yields of products.

Fe3O4@SnO2/SO4-2 was prepared and applied as a heterogeneous nanocatalyst to synthesize α-amino phosphonate derivatives. The reaction was performed under solvent-free conditions at 80 °C. Synthesized compounds were characterized by FT-IR, ¹HNMR, and 13C-NMR. Magnetic properties lead to easy separation and reusability for several times. The simplicity of the procedure, easy workup, short reaction time, high efficiency, and toxic solvent removal are considerable advantages.