Résumé: A set of nitrogen-based heterocycles derived from the quinoline ring as well as cyclohexanedione and dimedone cores were subjected to in vitro anticancer activity evaluation against four different cancerous cell lines namely; HCT116, A549, PC3, and MCF-7 respectively to colon, lung, prostate, and breast cancers. Compound 3g presented promising results exhibiting the best IC50 values among the investigated compounds for the four tested cell lines. In vitro results were supported with in silico studies including molecular docking simulation in order to learn more about the binding mode of the studied derivatives with relevant drug targets in cancer treatment, namely; anaplastic lymphoma kinase and cyclin-dependent kinase 2. Compound 3g showing the best in vitro results exhibited the most promising docking scores among the studied compounds. Moreover, molecular dynamics simulation was performed to the best ligand studying its stability inside the selected enzymes. Furthermore, a DFT study was performed to investigate the structural composition, electron density, and reactivity of tested compounds to identify the most important parts of the derivatives and elaborate a structure–activity relationship

Résumé: A series of 14 acridine derivatives was synthesized from the condensation of different β-enaminones and aromatic aldehydes, under microwave irradiation in catalyst-free conditions. The synthesis was favored for its rapidity, good yields, and environmental friendliness as it avoided the use of dangerous products and involved the employment of simple reactants and benign reaction conditions. The introduction of an ortho substituent in the aromatic aldehyde ring led to novel acridine-derived molecules containing hydroxyl groups. The structure of imino-acridine 5d was fully determined using XRD method and confirmed the obtainment of both E-(R) and E-(S) isomers. In vitro studies were performed to evaluate the antioxidant capacity of the synthesized compounds as well as the anti-urease activity. The results showed that the novel hydroxylated compound 5m was potent in the DPPH antioxidant test (IC50 = 0.99 ± ¦0.13 µmol/mL) and gave an interesting activity against urease enzyme with an IC50 of 0.03 ± ¦0.01 µmol/mL that is considered better than the standard molecule thiourea (IC50 = 0.10 ± ¦0.004 µmol/mL). An in silico investigation that consisted of a molecular docking study and molecular dynamics simulation was completed to predict the binding mode of the novel hydroxylated compound 5m towards active sites of both xanthine oxidase and urease enzymes as antioxidant and anti-urease targets, respectively. Furthermore, we employed DFT calculations to analyze the electronic and geometric properties of the optimal compound, 5m The HOMO and LUMO band gap energies, as well as the molecular electrostatic potential surface, were deduced for the stable structure

Résumé: This review discusses recent progress in the most significant synthetic approaches involving transformations under the Mitsunobu reaction. The Mitsunobu reaction entails the "redox" condensation of an acidic pronucleophile ‘Nu-H’ and an electrophilic primary or secondary alcohol, facilitated by stoichiometric amounts of phosphines and azodicarboxylate reagents. Widely utilized for dehydrative oxidation–reduction condensation, this reaction shows synthetic utility through its tolerance of a broad range of acidic pronucleophiles, including carboxylic acids, pro-imides, hydroxamates, phenols, thiols, fluorinated alcohols, oximes, thioamides, pyridinium and imidazolium salts, pyrimidine bases, α-ketoesters, and trimethylmethane tricarboxylate, thereby yielding a variety of functional and potentially biologically active compounds. The purpose of this review is to focus on recent advances and applications of Mitsunobu reaction chemistry, particularly from 2010 to 2024. In addition to discussing newer reagents that facilitate purification, we will describe contemporary applications of this chemistry, especially concerning the synthesis of potential biological compounds and their precursors. This focus review of the Mitsunobu reaction summarizes its origins, the current understanding of its mechanism, and recent improvements and applications. We aim for this work to serve as a useful resource for scientists working in this research domain

Résumé: 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-β-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.

Résumé: 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.

Résumé: This study investigates the synthesis of hydroxyapatite nanoparticles via aqueous precipitation at pH 9 and Ca/P molar ratio of 1.67, exploring the effects of various synthesis parameters. Moreover, porous hydroxyapatite scaffolds were created using a pore-forming agent. These parameters’ effects on the crystal structure, chemical composition, morphology, porosity, and pore size of hydroxyapatite powders and porous scaffolds were determined by various analytical techniques such as x-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), simultaneous thermal analysis (TGA/DSC), electron microscopy (SEM), pycnometry, and optical microscopy (OM). The XRD results revealed good crystallization of the hydroxyapatite with the formation of TCP and TTCP secondary phases resulting from the decomposition of hydroxyapatite (HA). The FTIR spectra of sintered HA confirmed the presence of the main absorption bands corresponding to phosphate and hydroxide groups with different peaks in intensity. The TGA/DSC analysis confirmed the results previously obtained by FTIR and XRD. SEM analysis showed the formation of various shapes of hydroxyapatite nanoparticles. According to different synthesis parameters, a porous HA scaffold up to 61% porosity can be prepared using ammonium bicarbonate as a pore-forming agent

Résumé: In this paper, we have attempted a theoretical calculation of some plant-isolated compounds as potential inhibitors of oxidative stress and Advanced Glycation Endproducts (AGEs). Herein, theoretical reactivity indices based on the CDFT theory were computed to explore the reactivity of five isolated products from Calophyllum flavoramulum. Global reactivity indices based on HOMO and LUMO energy such as electronic chemical potential, hardness, electrophilicity and the local reactivity descriptors Parr function, molecular electrostatic potentials(MEP), electrostatic potential (ESP) and thermodynamic parameters for the studied compounds are computed and discussed using DFT method and two functionals B3LYP and CAM-B3LYP with 6-31 G(d,p) basis set. The free radical scavenging activity mechanisms (HAT, SET-PT, and SPLET) of some of the isolated products with DPPH are also presented in this work. SET-PT mechanism of the antiradical activity is found to be thermodynamically favorable. Furthermore, a molecular docking study with RAGE receptor and AtGSTF2 enzyme was conducted, in which flavonoids 4 and 5 show a low binding affinity with −8.42 and −10.49 kcal/mol for RAGE, −8.67 and −9.00 kcal/mol for AtGSTF2. After the encouraging outcomes from the molecular docking study, the 4-AtGSTF2 and 5-RAGE complex were subjected to 200 ns molecular dynamics simulation using Desmond, where both studied systems exhibited remarkable stability throughout the 200 ns simulations. Also, the MM-GBSA method was measured by calculating the binding free energy using the individual energy components. Finally, the ADMET predictions were assessed to anticipate the behavior of a drug candidate within the human body.

Résumé: The development of novel, clean, and efficient methods for the preparation of compounds is a major research focus in organic chemistry at the moment. In this context, copper bromide (CuBr) has been utilized as a heterogeneous catalyst for a highly efficient, eco-sustainable, and greener synthesis of β-enaminone derivatives by condensation of 1,3-diketones with various primary amines at room temperature under ultrasound irradiation and solvent-free conditions. The structure of the synthesized compounds was confirmed by 1H, 13C NMR spectroscopy, IR spectroscopy, and elemental analysis. The desired products were obtained in excellent yields (90–98%) within short reaction times (20–50 min).

Résumé: A computational Petra/Osiris/Molinspiration/DFT(POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of series of oxazaphosphinanes derivatives 1a-1f containing potential antifungal O,N-pharmacophore. A molecular docking study was performed in order to evaluate synthesized compounds, their possible antifungal properties, and their interactions in the binding site. Molecular docking studies revealed that the compounds 1a-1f have the potential to become lead molecules in the drug discovery process. The six compounds 1a–1f analyzed here were previously synthesized by our group.

Résumé: 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

Résumé: In the present study, we investigated the cytotoxic activity of three compounds prepared starting from amino acids. These derivatives were evaluated for their in vitro antitumor activity against human cell lines (PRI, K562 and JURKAT). Their cytotoxicity was also evaluated at different concentrations on several cell lines. On the other hand, DFT calculation has been used to analyze the electronic and geometric characteristics. The HOMO, LUMO and gap energies were also deduced for the stable structure for each compound. These results will be correlated with the experimental values. The bioinformatic POM (Petra/Osiris/Molinspiration) analyses of the relative cytotoxicity of these derivatives are reported in comparison to Chlorambucil.

Résumé: In this paper, the structural analysis of two novel derivatives of N-Acylsulfonamides (1a-1b) has been made. Packings of the two crystal structures presented herein are the results of individually weak but synergistic non covalent interactions like typical NH... O=(C or S) hydrogen bonds or π/π stacking effects. DFT calculation of molecular electrostatic potentials

Résumé: An efficient protocol was developed for the synthesis of N-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 N-sulfonylimines was accomplished from various N-sulfonamides and benzaldehyde.

Résumé: An efficient protocol was developed for the synthesis of N-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 N-sulfonylimines was accomplished from various N-sulfonamides and benzaldehyde.

Résumé: A simple, efficient and environmentally benign method for the synthesis of α-hydroxyphosphonates by reaction of an aldehyde or a ketone, and trialkylphosphite is effectively accomplished under ultrasound irradiation and solvent-free and catalyst-free conditions. This rapid method produces α-hydroxyphosphonates in high yields and short reaction times.

Résumé: A convenient method for the synthesis of new series of N-acylsulfonamide containing oxazolidin-2-one moiety starting from chlorosulfonyl isocyanate and chiral oxazolidinones in two steps (carbamoylation and sulfamoylation), is described. The starting oxazolidinones were obtained in two steps starting from amino acids by reduction with NaBH4 then cyclization in the presence of carbonate diethyl. The synthesis of N-acylsulfonamide oxazolidin-2-ones derivatives has been carried out in excellent isolated yields. The structures of all synthesized compounds were unambiguously confirmed by usual spectroscopic methods 1H NMR, 13C NMR, IR, EA and MS

Résumé: A new series of N, -bis-oxazolidinones-sulfone and 5-chloromethylsulfamoyl-oxazolidin-2-ones have been synthesized in three steps (carbamoylation, sulfamoylation and cyclization) starting from 1,3-dichloroporopan-2-ol, chlorosulfonyl isocyanate and primary or secondary amines. Synthesis has been carried out following simple methodology in excellent isolated yields. The structure and purity of the original compounds were confirmed by IR, NMR, and MS. The compounds were evaluated for their in vitro antibacterial activity against some Gram-positive bacteria; Staphylococcus aureus and Gram-negative bacteria; Escherichia Coli, Klebsiella pneumonieae, Acinetobacter, Pseudomonas aeruginosa, Enterococcus, Salmonella sp. The compounds showed moderate to good antibacterial activity.

Résumé: An efficient, eco-sustainable and greener procedure for the synthesis of α-ureidophosphonates via a one-pot three-component reaction of aldehydes, urea/thiourea and triethylphosphite or diethylphosphite using ultrasonic irradiation under solvent- and catalyst-free conditions at 75°, is developed. The desired products were obtained in excellent yields within short reaction times (15–30 min). Crystals of diethyl[α-ureido-(4-methylphenyl)]methyl phosphonate suitable for X-ray study have been obtained after recrystallization in a mixture of diethyl ether and n-hexane. The detailed analysis of the molecular and crystal structure is presented.

Résumé: A rapid and efficient solvent-free one-pot synthesis of novel oxazaphosphinane is described under ultrasound irradiation. This reaction was carried out through a three-component condensation reaction of amino alcohol, aromatic aldehyde, and triethyl phosphite. Ultrasonic effects were established with many advantages, including high yields, shorter reaction times, easy and quick isolation of the products. The newly synthesized compounds were systematically characterized by IR, 1H NMR, 13C NMR, 31P NMR, MS, and elemental analysis.

Résumé: The oxazolidin-2-ones are key intermediates in the synthesis of various compounds of interest in terms of reactivity. So, several aminoalcohols were prepared from oxazolidinone. The oxazolidinone may also be used as an intermediate in the preparation of peptidosulfonamide similar sulfonated a natural or synthetic peptide. The reactive condition typical for conversion of the cycle oxazolidinone from the aminoalcohol involves the use of a base hydroxyl, water and different types of organics co-solvents.

Résumé: The phosphorylation reaction of various N-acylamines, N-acylaminoesters N-acylaminoalcohols and N-acylsulfonamides with trimethylphosphite or triethylphosphite was effectively promoted under ultrasound irradiation, solvent and catalyst free conditions to produce the corresponding amidophosponate. This rapid method produced the products in short reaction times (5–15 min) and excellent yields (75–90%). This technique at a frequency of 40 kHz, strongly accelerates the process of formation of P–C bonds compared to the classic Arbuzov reaction.

Résumé: Natural products, particularly flavonoids, which possess medicinal properties such as anticancer, anti-inflammatory, and antioxidant effects are known to inhibit the xanthine oxidase (XO) enzyme, which plays a key role in purine metabolism and generates reactive oxygen species (ROS). Inhibiting XO may help manage diseases associated with uric acid accumulation and ROS production. Molecular docking was performed to analyze the interactions of two benzoxanthone-flavonoid compounds, Artonin E and (+)-Artobiloxanthone, with the XO enzyme. These compounds demonstrated excellent stability within the site active of the XO enzyme, with estimated docking scores of− 9.64 and− 7.99 kcal/mol, respectively, and formed significant interactions, similar to those observed in the quercetin-XO complex. Additionally, ADMET analyses suggest that these compounds have promising therapeutic potential.

Résumé: Carbonic anhydrases (CA) are a group of zinc-containing enzymes involved in many physiological processes with their role in the maintenance of the equilibrium between bicarbonate and CO2 levels. Human carbonic anhydrases (hCA) are recognized as important drug targets due to their major implication in the development of diseases including cancer. Sulfanilamide derivatives were widely studied and showed remarkable efficiency in inhibiting carbonic anhydrases; with the presence of SO2NH2 in their structure. Therefore, sulfonamide moiety is considered as the leading scaffold in the search for new hCA inhibitors. Moreover, the introduction of an enaminone to sulfonamide-based CA inhibitors showed an enhancement of the inhibitory activity. In this context, we were interested in the in silico investigation of benzenesulfonamide derivatives containing β-enaminone that were synthesized from dicarbonyl compounds and sulfanilamide under microwave irradiation. The in silico assessment includes a molecular docking simulation against hCA II (PDB: 2AW1). The docked ligands showed good docking score values (−8.099 and −7.053 kcal.mol−1), which indicates a good stability of the studied compounds within the active site. Further, significant interactions with the residues of the active site was observed including a metal coordination with the Zn 262, an H-bond with Thr 199, and a pi-pi stacking with the side chain of His94, which are considered as the key interactions for a CA inhibition. A complementary in silico study that involves an ADMET prediction was performed to learn more about the pharmacokinetics properties and the toxicity of the products in order to comprehend their ability to become drug-candidates

Résumé: Heterocyclic chemistry plays a crucial role in drug design and the development of novel biologically active compounds. Many synthetic products with diverse pharmacological benefits feature heterocyclic structures, making them essential in the medicinal field. One notable class of heterocycles is 4-hydroxyquinolin-2-one, which hold significant importance in medicinal chemistry. 4-hydroxyquinolin-2-ones find wide-ranging applications as therapeutic agents, exhibiting antibacterial, anticancer, antiproliferative, analgesic, antiallergenic, and antitubercular activities. They have also been identified as antagonists of the cannabinoid type 2 receptor and modulators of glycogen synthase kinase GSK-3. To continue our research into the synthesis of new bioactive agents; we synthesized and characterized a derivative of 4-hydroxyquinolin-2-one. This synthesis involved a two-step process: initially, we produced an enaminone by condensing cyclohexylamine with dimedone, employing ultrasonic irradiation and CuBr as a catalyst. Subsequently, in the second step, we reacted the prepared enaminone with diethylmalonate, utilizing microwave irradiation. Moreover, a molecular docking study was performed to explore the binding mode of studied compound within the active site of Eg5 enzyme. The results showed a good stability of the 4-hydroxyquinoilone inside the cavity with an interesting docking score. Additionally, we conducted an in-silico investigation to predict the drug-likeness and ADME (Absorption, Distribution, Metabolism, and Excretion) properties of the compound, utilizing MolSoft and SwissADME as precise predictive tools