Quantum computational calculations of novel N-sulfonylimine derivatives

A computer model based on the density functional theory (DFT) was developed for the identification of the physico-chemical parameters governing the bioactivity of novel N-sulfonylimine derivatives 1a-1f containing a potential antibacterial pharmacophore sulfonamide unit. This study was performed using DFT / B3LYP with 6-31G (d, p) basis set. Information on the size, shape, charge density distribution, and site of chemical reactivity of molecules 1a-1f was obtained by mapping the electron density isosurface with the electrostatic potential surface. The energies of frontier molecular orbitals and the LUMO-HOMO energy gap are measured to explain electronic transitions. To find the most reactive sites of the molecules studied, condensed Fukui functions were also calculated. The six compounds 1a-1f analyzed here were previously synthesized by our group. Un modèle informatique basé sur la théorie fonctionnelle de la densité (DFT) a été développé pour l'identification des paramètres physico-chimiques régissant la bioactivité de nouveaux dérivés de N-sulfonylimine 1a-1f contenant une pharmacophore antibacterien potential sulfonamide.  Cette étude a été réalisée en utilisant la méthode DFT / B3LYP avec la base 6-31G (d, p). Des informations sur la taille, la forme, la distribution de densité de charge et le site de réactivité chimique des molécules 1a-1f ont été obtenues en cartographiant l'isosurface de densité électronique avec la surface de potentiel électrostatique. Les énergies des orbitales moléculaires frontières et l'écart énergétique LUMO-HOMO sont mesurés pour expliquer les transitions électroniques. Pour trouver les sites les plus réactifs des molécules étudiées, des fonctions de Fukui condensées ont également été calculées. Les six composés 1a-1f que nous avonts analysés ont été préalablement synthétisés par notre groupe

New efficient synthesis, spectroscopic characterization, and X-ray analysis of novel β-enaminocarboxamide derivatives

International audienceA new series of β-enaminocarboxamide was synthesized via the addition of chlorosulfonyl isocyanate to β-enaminones. The prepared intermediates were converted to corresponding β-enaminocarboxamides by removal of the chlorosulfonyl group using methanol. The resulting compounds were obtained in excellent yields in the range of (80-92%) and were characterized by 1 H, 13 C, HMBC, HSQC NMR spectroscopy, and IR spectroscopy as well as elemental analysis. 1 H-NMR spectrum showed a non-equivalence of the primary amide protons which was due to H-bonding. β-enaminocarboxamide 5h was obtained as a crystal and was subjected to X-ray analysis. Results showed that 5h crystallizes in the monoclinic crystal system with C2/c space group and the ORTEP confirmed the presence of intramolecular H-bonds

A practical and green approach towards synthesis of new <i>N</i>-sulfonylimines under ultrasound irradiation

<p>An efficient protocol was developed for the synthesis of <i>N</i>-sulfonylimines under environment friendly conditions. Ultrasonic energy was employed to obtain the desired products in excellent yields with high purity under solvent- and catalyst-free conditions. The synthesis of new <i>N</i>-sulfonylimines was accomplished from various <i>N</i>-sulfonamides and benzaldehyde.</p> <p>The structures of the synthesized compounds are confirmed by elemental analysis as well as by ¹H, ¹³C NMR spectral data, IR and MS.</p

A convenient synthesis, in silico study and crystal structure of novel sulfamidophosphonates: Interaction with SARS-CoV-2

International audienceA one-pot synthetic strategy was developed for the synthesis of novel sulfamidophosphonates via a threecomponent Kabachnik-Fields reaction of sulfanilamide, triethyl phosphite, and various aldehyde using ultrasound irradiation. Seven organophosphorus derivatives were synthesized with high yields through this newly developed method. The target compounds were characterized by 1 H, 31 P, 13 C NMR, and IR. The molecular structure of 4a was obtained by X-ray diffraction on the monocrystal. Crystal belongs to the orthorhombic system with space groups Pbca. Insight into the binding mode of the synthesized compounds (ligand) into the binding sites of SARS-CoV2 (PDF code: 5R80) was provided by docking studies, performed with the help of Maestro 9.0 docking software

Novel pseudonucleosides and sulfamoyl-oxazolidinone <i>β</i>-<i>D</i>-glucosamine derivative as anti-COVID-19: design, synthesis, and <i>in silico</i> study

International audienceNew pseudonucleosides containing cyclic sulfamide moiety and sulfamoyl b-D-glucosamine derivative are described. These pseudonucleosides are synthesized in good yields starting from chlorosulfonyl isocyanate and b-D-glucosamine hydrochloride in five steps; (protection, acetylation, removal of the Boc group, sulfamoylation, and cyclization). Further, novel glycosylated sulfamoyloxazolidin-2-one is prepared in three steps; carbamoylation, sulfamoylation, and intramolecular cyclization. The structures of the synthesized compounds were confirmed by usual spectroscopic and spectrometric methods NMR, IR, MS, and EA. Interesting molecular docking of the prepared pseudonucleosides and (Beclabuvir, Remdesivir) drugs with SARS-CoV-2/M pro (PDB:5R80) was conducted using the same parameters for a fair comparison. A low binding affinity of the synthesized compounds compared to the Beclabuvir and other analysis showed that pseudonucleosides have the ability to inhibit SARS-CoV-2. After the motivating results of molecular docking study, the complex between the SARS-CoV-2 M pro and compound 7 was subjected to 100 ns molecular dynamics (MD) simulation using Desmond module of Schrodinger suite, during which the receptor-ligand complex showed substantial stability after 10 ns of MD simulation. Also, we studied the prediction of absorption, distribution, properties of metabolism, excretion, and toxicity (ADMET) of the synthesized compounds

Synthesis, In silico study (DFT, ADMET) and crystal structures of novel sulfamoyloxy-oxazolidinones: Interaction with SARS-CoV-2

International audienceA new series of sulfamoyloxyoxazolidinone (SOO) derivatives have been synthesized and characterized by single-crystal X-ray diffraction, NMR, IR, MS and EA. Chemical reactivity and geometrical characteristics of the target compounds were investigated using DFT method. The possible binding mode between SOO and Main protease (Mpro) of SARS-CoV-2 and their reactivity were studied using molecular docking simulation. Single crystal X-ray diffraction showed that SOO crystallizes in a monoclinic system with P 2 1 space group. The binding energy of the SARS-CoV-2/Mpro-SOO complex and the calculated inhibition constant using docking simulation showed that the active SOO molecule has the ability to inhibit SARS-CoV2. We studied the prediction of absorption, distribution, properties of metabolism, excretion and toxicity (ADMET) of the synthesized molecules

Synthesis, in silico study, and biological evaluation of cyclosulfamide derivatives as new anticholinesterase inhibitors

International audienceAfter the great spread of Alzheimer's disease (AD) in the past few years, many researchers directed their work toward developing an effective treatment for this disease and to discovering very advanced drugs. Cyclosulfamides are considered as versatile pharmacophores in the construction of new molecules with excellent activities. Therefore, a series of cyclosulfamide have been synthesized and evaluated as anti-Alzheimer agents through in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition. Most of tested compounds showed an average inhibitory activity against two targeted enzymes compared with the reference ligand. Specifically, 10a showed the best inhibition of AChE enzyme with an IC50=45.30±0.88µM; while 4a exhibited the most potent BuChE enzyme inhibition with an IC50=52.87±3.73µM. Further, we were able to determine a feasible binding mode for cyclosulfamide derivatives owing to molecular docking studies, which offered prospective evidence to identify significant interactions between the active site of AChE and the synthesized ligands. Following the encouraging findings of the molecular docking investigation, the complex AChE-10a was put through a 100ns Desmond of Schrodinger simulation of molecular dynamics (MD), during which the receptor-ligand combination showed significant stability after 10 ns of MD simulation

Novel N-acylsulfamoyl-oxazolidin-2ones: Synthesis, antitumor activity, X-ray crystallographic study, molecular docking and POM analyses

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Ninhydrins inhibit carbonic anhydrases directly binding to the metal ion

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