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The design, synthesis, X-ray structural, and biological evaluation of a series of highly potent HIV-1 protease inhibitors are reported herein. These inhibitors incorporated novel cyclohexane-fused tricyclic bis-tetrahydrofuran as P2 ligands in combination with a variety of P1 and P2’-ligands. The inhibitor with a difluoromethylphenyl P1 ligand and a cyclopropylaminobenzothiazole P2’ ligand exhibited the most potent antiviral activity. Also, it maintained potent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The corresponding inhibitor with an enantiomeric ligand was significantly less potent in these antiviral assays. The new P2 ligands were synthesized in optically active form using enzymatic desymmetrization of meso-diols as the key step. To obtain molecular insight, two high resolution X-ray structures of inhibitor-bound HIV-1 protease were determined and structural analyses have been highlighted.

Here, we report the synthesis, structure-activity relationship studies, enzyme inhibition, antiviral activity, and X-ray crystallographic studies of 5-chloropyridinyl indole carboxylate derivatives as a potent class of SARS-CoV-2 chymotrypsin-like protease inhibitors. Compound 1 exhibited a SARS-CoV-2 3CLpro inhibitory IC50 value of 250 nM and an antiviral EC50 value of 2.8 µM in VeroE6 cells. Remdesivir, an RNA-dependent RNA polymerase inhibitor, showed an antiviral EC50 value of 1.2 µM in the same assay. Compound 1 showed comparable antiviral activity with remdesivir in immunocytochemistry assays. Compound 7d with an N-allyl derivative showed the most potent enzyme inhibitory IC50 value of 73 nM. To obtain molecular insight into the binding properties of these molecules, X-ray crystal structures of compounds 2, 7b, and 9d-bound to SARS-CoV 3CLpro were determined, and their binding properties were compared.

We report the design and synthesis of a series of new 5-chloropyridinyl esters of salicylic acid, ibuprofen, indomethacin, and related aromatic carboxylic acids for evaluation against SARS-CoV-2 3CL protease enzyme. These ester derivatives were synthesized using EDC in the presence of DMAP to provide various esters in good to excellent yields. Compounds are stable and purified by silica gel chromatography and characterized using 1H-NMR, 13C-NMR, and mass spectral analysis. These synthetic derivatives were evaluated in our in vitro SARS-CoV-2 3CLpro inhibition assay using authentic SARS-CoV-2 3CLpro enzyme. Compounds were also evaluated in our in vitro antiviral assay using quantitative VeroE6 cell-based assay with RNAqPCR. A number of compounds exhibited potent SARS-CoV-2 3CLpro inhibitory activity and antiviral activity. Compound 9a was the most potent inhibitor, with an enzyme IC50 value of 160 nM. Compound 13b exhibited an enzyme IC50 value of 4.9 µM. However, it exhibited a potent antiviral EC50 value of 24 µM in VeroE6 cells. Remdesivir, an RdRp inhibitor, exhibited an antiviral EC50 value of 2.4 µM in the same assay. We assessed the mode of inhibition using mass spectral analysis which suggested the formation of a covalent bond with the enzyme. To obtain molecular insight, we have created a model of compound 9a bound to SARS-CoV-2 3CLpro in the active site.

In this work, the interactions between simple carbon nanotubes (CNTs) and doped carbon nanotubes (DCNTs; with sulfur, boron, aluminum, silicon, phosphorus, or nitrogen) as good adsorbents with various ions such as Fe2 +, Na +, Ca2 +, Mg2 +, Cl−, CO32−, SO42−, and NO3− were fully considered through density functional theory (DFT), natural bond orbital (NBO), quantum theory of atoms in molecules (QTAIM) calculations. The adsorption energies (Ead) demonstrated that these ions could be adsorbed on the surface of the CNTs and DCNTs via the exothermic process, especially in the gas phase. QTAIM analysis confirmed that there are non-covalent interactions between these ions and CNT or DCNTs. The calculated energies illustrated that Si-CNTs and B-CNTs have the highest Ead values in the gas and solvent phase, respectively. Moreover, CNTs had the least Ead values in both phases and the best ion with the minimum Ead value in both phases is iron. Finally, population analyses were performed to obtain the reactivity parameters, molecular properties, bonding structural, and density of states (DOS) plots of all structures.

A convenient protocol for amide bond formation for electron deficient amines and carboxylic acids is described. Amide coupling of aniline derivatives has been investigated with a number of reagents under a variety of reaction conditions. The use of 1 equivalent of EDC and 1 equivalent of DMAP, catalytic amount of HOBt and DIPEA provided the best results. This method is amenable to the synthesis of a range of functionalized amide derivatives with electron deficient and unreactive amines.

The COVID‐19 pandemic caused by SARS‐CoV‐2 infection is spreading at an alarming rate and has created an unprecedented health emergency around the globe. There is no effective vaccine or approved drug treatment against COVID‐19 and other pathogenic coronaviruses. The development of antiviral agents is an urgent priority. Biochemical events critical to the coronavirus replication cycle provided a number of attractive targets for drug development. These include, spike protein for binding to host cell‐surface receptors, proteolytic enzymes that are essential for processing polyproteins into mature viruses, and RNA‐dependent RNA polymerase for RNA replication. There has been a lot of ground work for drug discovery and development against these targets. Also, high‐throughput screening efforts have led to the identification of diverse lead structures, including natural product‐derived molecules. This review highlights past and present drug discovery and medicinal‐chemistry approaches against SARS‐CoV, MERS‐CoV and COVID‐19 targets. The review hopes to stimulate further research and will be a useful guide to the development of effective therapies against COVID‐19 and other pathogenic coronaviruses., Effective antiviral treatment? The review highlights potential drug design targets against pathogenic coronaviruses, particularly Covid‐19 as well as past and recent progress towards the development of small‐molecule drug‐like compounds including protein‐X‐ray structure‐based design of cysteine protease inhibitors. Hopefully, the present review will stimulate development of much needed effective drugs against Covid‐19.

The detailed mechanisms for the initial steps of methanol to gasoline (MTG) process, up to 3-carbons products, were studied using DFT calculations and aluminum doped graphene (AG) as catalyst. During the study, the structures of the reactants, products, intermediates and transition states were optimized and confirmed by frequency and IRC calculations. The most of steps are energetically affordable with acceptable barrier energies. The best route (by considering both thermodynamic and kinetic values) was producing ethanol as intermediate and 1-propanol as 3-carbons product. In addition, the production of dimethyl ether and ethylene as intermediates and methyl ethyl ether as a product were energetically possible. This work proved the catalytic ability of AG for MTG process and the results could be employed in the future experimental studies regard to the developments of new catalysts for MTG process.

In this study, noncovalent interactions between Fluoxetine (FX) and different carbon nanotubes (CNTs) or sulfur doped carbon nanotubes (SCNTs) were fully considered using DFT, natural bond orbital (NBO) and molecular docking calculations. Two different CNTs (and SCNTs) with 7,7 and 8,8 chiralities were considered as the adsorbents and the adsorption of FX by these adsorbents were studied in two cases: into the nanotubes and on their surfaces. The results of DFT and NBO calculations proposed that the 8,8 nanotubes are more suitable adsorbents for FX because the energies of their adsorptions are minimum. Population: analyses were also proposed that the adsorption of FX by SCNTs lead to more changes in electronic and sensing properties than the adsorption by CNTs. Moreover, the adsorption energies, obtained from molecular docking calculations (using 94 different models), proposed that the adsorption of FX into (versus out of) the nanotubes, adsorption processes by double-walled or triple-walled (versus single-walled) nanotubes and the adsorption by nanotubes with 8,8 chiralities are the most favorable adsorption processes.

In this study, various xanthene derivatives have prepared efficiently through a simple method using choline chloride/tin(II) chloride (ChCl·2SnCl2) deep eutectic solvent (DES), alone, or in the presence of Fe3O4/ƛ-carrageenan/Zn(II) magnetic bionanocatalyst. In the employed procedure, 2-naphthol derivatives have mixed with aromatic or aliphatic aldehydes and the reactions have been completed in the presence of DES at 90 °C in 1.5 h. In addition, using DES/Fe3O4/ƛ-carrageenan/Zn(II), the reaction time was reduced to 30 min. The employed DES has been recycled four times without important loss of its activity.

In this work, various quinoline derivatives were prepared efficiently through a one-pot, three component synthesis using choline chloride/tin(II) chloride (ChCl·2SnCl2) deep eutectic solvent (DES) as a green catalyst. The procedure is free of using toxic solvents or catalyst and it could be categorized as a green method. In this procedure, aniline derivatives, aromatic aldehydes and enolizable aldehydes were mixed in the presence of DES that plays both roles of solvent and the reaction catalyst. Using this methodology, quinoline derivatives were synthesized simply at 60 °C in 2–3 h with high yields (54–97%). All products were purified by chromatography and recrystallization in ethanol. The employed DES have been recycled 4 time without important loss of its activity.

In this work, the interactions of S-doped single-wall carbon nanotubes (SCNTs) with rare gases (RGs) were fully considered using density functional theory (DFT), quantum theory of atom in molecule ...

The oxidative conversion of 1,4-dihydropyridines to give the corresponding pyridine derivatives in excellent yields was easily effected using the catalytic amount of NaI in combination with H2O2 (30%) as a green external oxidant. The process is highly green wherein the solid products are easily filtered out after the addition of ice-water to the reaction mixture. This non-transition metal catalyst is cost-effective, affords simple work-up and easy separation of the product.