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.

Novel N-acylsulfonamides: Synthesis, in silico prediction, molecular docking dynamic simulation, antimicrobial and anti-inflammatory activities.

Microbial resistance to drugs currently traded in the market is a serious problem in modern medicine. In this field of research, we synthesized a novel N-acylsulfonamides (NAS) derivatives starting from commercially available compounds; morpholine, isocyanate of chlorosulfonyl and alcohols. The in vitro antimicrobial potential of synthesized compounds was screened against 04 Gram-negative bacteria; Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, 02 Gram-positive bacteria: Streptococcus sp, Staphylococcus aureus and 07 yeasts and fungi: Candida albicans, Candida spp, Penicillum spp, Aspegillus sp, Aspergillus flavus, Fusarium sp, and Cladosporium spp. The results of inhibition growth were compared with standard antimicrobial drugs with the goal of exploring their potential antimicrobial activity. In addition, the anti-inflammatory activity of the synthesized compounds was determined in-vitro by protein denaturation method. The obtained bioactivity results were further validated by in silico DFT (Density Functional Theory), ADME (Absorption-Distribution-Métabolisation-Excrétion), molecular docking studies and molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.

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.

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

A 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.

Ninhydrins inhibit carbonic anhydrases directly binding to the metal ion.

Ninhydrins show extensive application in organic chemistry and agriculture whereas they have been poorly investigated as bioactive molecules for medicinal chemistry purposes. A series of ninhydrin derivatives was here investigated for the inhibition of human carbonic anhydrases (CAs, EC 4.2.1.1), based on earlier evidence that gem diols are able to coordinate the metal ion from the CA active site. Ninhydrins demonstrated a micromolar inhibitory action against CA I and IX (KIs in the range 0.57-68.2 µM) and up to a nanomolar efficacy against CA II and VII (KIs in the range 0.025-78.2 µM), validated isoforms as targets in several CNS-related diseases. CA IV was instead weakly or poorly inhibited. A computational protocol based on docking, MM-GBSA and metadynamics calculations was used to elucidate the putative binding mode of this type of inhibitors to CA II and CA VII. The findings of this study testify that such pharmacologically underestimated ligands may represent interesting lead compounds for the development of CA inhibitors possessing an innovative mechanism of action, i.e., mono- or bis-coordination to the zinc ion through the diol moiety.

QSAR Model of Indeno[1,2-b]indole Derivatives and Identification of N-isopentyl-2-methyl-4,9-dioxo-4,9-Dihydronaphtho[2,3-b]furan-3-carboxamide as a Potent CK2 Inhibitor.

Casein kinase II (CK2) is an intensively studied enzyme, involved in different diseases, cancer in particular. Different scaffolds were used to develop inhibitors of this enzyme. Here, we report on the synthesis and biological evaluation of twenty phenolic, ketonic, and para-quinonic indeno[1,2-b]indole derivatives as CK2 inhibitors. The most active compounds were 5-isopropyl-1-methyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4h and 1,3-dibromo-5-isopropyl-5,6,7,8-tetrahydroindeno[1,2-b]indole-9,10-dione 4w with identical IC50 values of 0.11 µM. Furthermore, the development of a QSAR model based on the structure of indeno[1,2-b]indoles was performed. This model was used to predict the activity of 25 compounds with naphtho[2,3-b]furan-4,9-dione derivatives, which were previously predicted as CK2 inhibitors via a molecular modeling approach. The activities of four naphtho[2,3-b]furan-4,9-dione derivatives were determined in vitro and one of them (N-isopentyl-2-methyl-4,9-dioxo-4,9-dihydronaphtho[2,3-b]furan-3-carboxamide) turned out to inhibit CK2 with an IC50 value of 2.33 µM. All four candidates were able to reduce the cell viability by more than 60% after 24 h of incubation using 10 µM.

Synthesis, Spectroscopic Characterization, and In Vitro Antibacterial Evaluation of Novel Functionalized Sulfamidocarbonyloxyphosphonates.

Several new sulfamidocarbonyloxyphosphonates were prepared in two steps, namely carbamoylation and sulfamoylation, by using chlorosulfonyl isocyanate (CSI), α-hydroxyphosphonates, and various amino derivatives and related (primary or secondary amines, ß-amino esters, and oxazolidin-2-ones). All structures were confirmed by ¹H, 13C, and 31P NMR spectroscopy, IR spectroscopy, and mass spectroscopy, as well as elemental analysis. Eight compounds were evaluated for their in vitro antibacterial activity against four reference bacteria including Gram-positive Staphylococcus aureus (ATCC 25923), and Gram-negative Escherichia coli (ATCC 25922), Klebsiella pneumonia (ATCC 700603), Pseudomonas aeruginosa (ATCC 27853), in addition to three clinical strains of each studied bacterial species. Compounds 1a⁻7a and 1b showed significant antibacterial activity compared to sulfamethoxazole/trimethoprim, the reference drug used in this study.