Zinc acetate-catalyzed, green and efficient synthesis of xanthene derivatives under ultrasound irradiation: X-ray crystallographic analysis and in silico study.

A simple, one-pot method using zinc acetate and ultrasound irradiation has been developed to synthesize xanthene derivatives from cyclic diketones and aromatic aldehydes, yielding good to excellent results. This method offers advantages like mild conditions, high atom economy, easy isolation, and a recyclable catalyst. All xanthene derivatives, including two new molecules, were confirmed using standard spectroscopic methods, with X-ray crystallographic data provided for compound 3r. The synthesized molecules were shown to inhibit the VEGFR-2 enzyme, confirmed by molecular docking studies. A 200 ns molecular dynamics simulation validated these findings, showing significant stability for the 3e-VEGFR-2 complex after 1 ns and the 3p-VEGFR-2 complex for 8 ns. DFT calculations were used to analyze electronic and geometric properties, including HOMO and LUMO bandgap energies and molecular electrostatic potential surfaces. Additionally, the absorption, distribution, metabolism, and excretion (ADME) properties of the synthesis compounds were assessed.

Phytochemical on-line screening and in silico study of Helianthemum confertum: antioxidant activity, DFT, MD simulation, ADME/T analysis, and xanthine oxidase binding.

Seven components from the methanol extract of the aerial part of the endemic species Helianthemum confertum were isolated and identified for the first time. Investigating this species and its separated components chemical make-up and radical scavenging capacity, was the main goal. Using an online HPLC-ABTS˙+ test, ORAC, and TEAC assays, the free radical scavenging capacity of the ethyl acetate extract was assessed. The fractionation of these extracts by CC, TLC, and reverse-phase HPLC was guided by the collected data, which was corroborated by TEAC and ORAC assays. Molecular docking studies, DFT at the B3LYP level, and an examination of the ADME/T predictions of all compounds helped to further clarify the phytochemicals' antioxidant potential. Isolation and identification of all components were confirmed through spectroscopy, which revealed a mixture (50-50%) of para-hydroxybenzoic acid 1 and methyl gallate 2, protocatechuic acid 3, astragalin 4, trans-tiliroside 5, cis-tiliroside 6, contaminated by trans-tiliroside and 3-oxo-α-ionol-ß-d-glucopyranoside 7, as well as two new compounds for the genus Helianthemum (2 and 7). With a focus on compounds 1, 2, 3, and 4, the results clearly showed that the extract and the compounds tested from this species had a high antioxidant capacity. Within the xanthine oxidase enzyme's pocket, all of the components tested showed strong and stable binding. In light of these findings, the xanthine oxidase/methyl gallate 2 complex was simulated using the Desmond module of the Schrodinger suite molecular dynamics (MD) for 100 ns. Substantially stable receptor-ligand complexes were observed following 1 ns of MD simulation.

An attempt to prepare sulfonyl analogues of fotemustine: unexpected rearrangement to sulfamate during nitrosation step.

This paper describes a flexible strategy to access diethyl ((((N-(2-chloroethyl)-N-nitrososulfamoyl)amino)arylmethyl) phosphonates, as aryl analogues of fotemustine. The new aryl sulfamidophosphonates prepared from 2-chloroethylamine were successfully obtained under eco-environmental conditions using ultrasound irradiation. These compounds did not produce the expected nitroso analogues of fotemustine after the nitrosation reaction but the corresponding sulfamates which were fully characterized. Some attempts to understand this rearrangement reaction were conducted, and particularly the corresponding nitrosoureas analogues could be isolated with good yield. The novel sulfonamidophosphonates as well as their sulfamate derivatives were evaluated for their cytotoxic effect on a panel of tumor cells.

BiCl3-catalyzed green synthesis of 4-hydroxy-2-quinolone analogues under microwave irradiation.

Traditional chemical synthesis, which involves the use of dangerous protocols, hazardous solvents, and toxic products and catalysts, is considered environmentally inappropriate and harmful to human health. Bearing in mind its numerous drawbacks, it has become crucial to substitute conventional chemistry with green chemistry which is safer, more ecofriendly and more effective in terms of time and selectivity. Elaborating synthetic protocols producing interesting new compounds using both microwave heating and heterogeneous non-toxic catalysts is acknowledged as a green approach that avoids many classical chemistry-related problems. In the current study, ß-enaminones were used as precursors to the synthesis of modified 4-hydroxy-2-quinolone analogues. The synthesis was monitored in a benign way under microwave irradiation and was catalyzed by bismuth chloride III in an amount of 20 mol%. This method is privileged by using a non-corrosive, non-toxic, low-cost and available bismuth Lewis acid catalyst that has made it more respectful to the demands of green chemistry. The synthesized compounds were obtained in moderate to good yields (51-71%) and were characterized by 1H, 13C NMR, and IR spectroscopy as well as elemental analysis. Compound 5i was subjected to a complete structural elucidation using the X-ray diffraction method, and the results show the obtention of the enolic tautomeric form.

In vitro antitumor activity, molecular dynamics simulation, DFT study, ADME prediction, and Eg5 binding of enastron analogues.

The objective of this study is to evaluate a series of molecules based on cyclosulfamide as potential anticancer agents. Additionally, the study aims to analyze the obtained results through in silico studies; by conducting experiments and utilizing theoretical methods. In this context, we investigated the cytotoxic activity of enastron analogues on three human cell lines PRI (lymphoblastic cell line) derived from B-cell lymphoma. JURKAT (ATCC TIB-152) acute T cell leukaemia and K562 (ATCC CLL-243) is a chronic myelogenous leukaemia. Most of the tested compounds showed good inhibitory activity compared with the reference ligand (chlorambucil). The 5a derivative demonstrated the strongest effect against all cancer cells used. Furthermore, molecular docking simulations of the Eg5-enastron analogue complex revealed that studied molecules have the ability to inhibit the Eg5 enzyme, as evidenced by their calculated docking score. Following the promising results from the molecular docking study, the complex Eg5-4a underwent a 100 ns molecular dynamics simulation using Desmond. During the simulation, the receptor-ligand pairing demonstrated substantial stability after the initial 70 ns. In addition, we used DFT calculations to analyze the electronic and geometric characteristics of the studied compounds. The HOMO and LUMO band gap energies, and the molecular electrostatic potential surface were also deducted for the stable structure of each compound. Also, we studied the prediction of absorption, distribution, metabolism and excretion (ADME) of the compounds.

Novel pseudonucleosides and sulfamoyl-oxazolidinone ß-D-glucosamine derivative as anti-COVID-19: design, synthesis, and in silico study.

New pseudonucleosides containing cyclic sulfamide moiety and sulfamoyl ß-D-glucosamine derivative are described. These pseudonucleosides are synthesized in good yields starting from chlorosulfonyl isocyanate and ß-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/Mpro (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 Mpro 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.Communicated by Ramaswamy H. Sarma.

A new class of heterocycles: 1,4,3,5-oxathiadiazepane 4,4-dioxides.

This work reports the synthesis of novel 1,4,3,5-oxathiadiazepanes 4,4-dioxides from the reaction of N'-benzyl-N-(2-hydroxyethyl)-sarcosine or proline sulfamide with aromatic aldehydes under acid catalysis. To prepare the starting materials N-Boc-sulfamide derivatives of sarcosine or proline were alkylated with benzyl alcohol under Mitsunobu reaction conditions, the Boc group was removed chemoselectively by acidolysis, and the resulting product reduced to the corresponding alcohol in good yields.

N-tert-Butoxycarbonylation of Structurally Diverse Amines and Sulfamides under Water-Mediated Catalyst-Free Conditions.

A simple, efficient, and eco-friendly protocol for the N-Boc protection of the amine moiety in a variety of compounds with di-tert-butyl dicarbonate under water-acetone catalyst-free conditions is described. The corresponding monocarbamate is obtained in excellent yields on short reaction times. No competitive side reactions such as isocyanate urea and O-Boc were observed. This method represents a reasonable alternative to the previous reported protection procedures.

1,2,3,4-Tetra-hydro-isoquinoline-2-sulfonamide.

The title compound, C(9)H(12)N(2)O(2)S, is a useful precursor of a variety of modified sulfonamide mol-ecules. Due to the importance of these mol-ecules in biological systems (antibacterials, antidepressants and many other applications), there is a growing inter-est in the discovery of new biologically active compounds. In the title compound, the mol-ecules are linked by N-H⋯O inter-molecular hydrogen bonds involving the sulfonamide function to form an infinite two-dimensional network parallel to the (001) plane.

New pseudonucleosides containing chiral oxazolidin-2-ones and cyclosulfamides as aglycones: synthesis and antiviral evaluation.

A series of chiral cyclosulfamides and oxazolidinon-2-ones have been synthesized starting from aminoacids. Regioselective substitution of these pseudopyrimidic heterocyles was carried out under Mitsunobu conditions. Best substitution results were obtained by preliminary deprotection of cyclosulfamides and their condensation with beta-D-ribofuranose. Chiral oxazolidin-2-ones were coupled directly with D-ribofuranose. All compounds were tested against HSV-2, VV and SV viruses. Two compounds 6b and 6e showed significant activities against HSV-type 1.

N,N'-SUBStituted 1,2,5 thiadiazolidine 1,1-dioxides: synthesis, selected chemical and spectral proprieties and antimicrobial evaluation.

The sulfamide functional group is increasingly relevant in both medicinal and bioorganic chemistry. We report here practical access to a series of N2,N5-substituted five-membered cyclosulfamides. The five-membered heterocyclic motif was prepared starting from proteogenic amino acids and chlorosulfonyl isocyanate via the Mitsunobu reaction. Selected chemical and spectral proprieties and the antimicrobial evaluation of these compounds are detailed.

Synthesis of new pseudonucleosides containing chiral cyclosulfamides as agycone.

A series of chiral cyclosulfamides have been synthesized in four steps, starting from N-benzoylaminoacids. Regioselective glycosylation of these pseudopyrimidic heterocycles was carried out after deprotection. Best glycosylation results were obtained by preliminary silylation of cyclosulfamides, and their condensation with a tetraacetylribofuranose and pentaacetylglucopyranose is described, which yielded the pseudonucleosides in a beta-anomeric configuration.