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In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC50 glucosidase= 97.12 ± 0.35 µM and IC50 amylase= 2.97 ± 0.01 μM). All compounds were then evaluated for their acute toxicity in vivo and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma., Authors thank all collaborators for their constant support and encouragement.

Six undescribed polyacetylenic caffeoyl amides, five known flavones and three known lignans were obtained from the fruits of the North African traditional medicinal plant Ammodaucus leucotrichus Coss.Durieu (Apiaceae). Isolation was achieved by a combination of chromatographic methods, and structures were established by extensive 1D and 2D NMR spectroscopy, mass spectrometry, electronic circular dichroism, and by GC-MS analysis of sugar derivatives. Polyacetylenic caffeoyl amides are reported for the first time as specialized metabolites.

Hydrodistilled volatile oils obtained from the fruits of Cuminum cyminum L. and Ammodaucus leucotrichus L., cultivated in Morocco, were analyzed by GC/FID and GC/MS. Twenty-one compounds repre- sen...

Two N-isonicotinoyl arylaldehyde hydrazones named N'-(4-fluorobenzylidene)isonicotinohydrazide (2a) N'-(4-methylbenzylidene)isonicotinohydrazide (2 b) have been synthesized and characterized utilizing spectroscopic techniques and X-ray diffraction. The s-cis isomeric geometry of 2a and 2 b is confirmed by comparing the observed stretching bond of the azomethine group with their corresponding calculated ones of s-cis and s-trans isomers for both 2a and 2 b. The s-cis geometry is in good accordance with the one obtained by X-ray techniques. The global and local electronic properties of 2a and 2 b were determined at the B3LYP/6-311 + G(d,p) level of theory. The Results reveal that the stability of s-cis isomers compared to s-trans ones is mainly refer to the intramolecular carbon-hydrogen bonding formed between lone pairs of the carbonyl group and the hydrogen atom of azomethine of 2.15 Å. The antidiabetic activity of 2a and 2 b is investigated by determining their potency to inhibit α-glucosidase. 2a and 2 b showed higher inhibitory toward α-glucosidase as compared to the reference drug acarbose. Molecular docking of 2a and 2 b into the active site of α-glucosidase showed that the higher inhibition efficiency of 2 b compared to 2a is mainly refers to the stability of 2 b-(α-glucosidase) complex compared with 2a-(α-glucosidase).

Copper is the third-most-produced metal globally due to its exceptional mechanical and thermal properties, among others. However, it suffers serious dissolution issues when exposed to corrosive mediums. Herein, two thiazolidinedione derivatives, namely, (Z)-5-(4-methylbenzylidene)thiazolidine-2,4-dione (MTZD) and (Z)-3-allyl-5-(4-methylbenzylidene)thiazolidine-2,4-dione (ATZD), were synthesized and applied for corrosion protection of copper in 3.5 wt.% NaCl medium. The corrosion inhibition performance of tested compounds was evaluated at different experimental conditions using electrochemical impedance spectroscopy (EIS), potentiodynamic polarization curves (PPC) and atomic force microscopy (AFM). EIS results revealed that the addition of studied inhibitors limited the dissolution of copper in NaCl solution, leading to a high polarization resistance compared with the blank solution. In addition, PPC suggested that tested compounds had a mixed-type effect, decreasing anodic and cathodic corrosion reactions. Moreover, surface characterization by AFM indicated a significant decrease in surface roughness of copper after the addition of inhibitors. Outcomes from the present study suggest that ATZD (IE% = 96%) outperforms MTZD (IE% = 90%) slightly, due to the presence of additional –C3H5 unit (–CH2–CH = CH2) in the molecular scaffold of MTZD.

Highlights • Ultrasound-assisted, one-pot green synthesis of new isoxazolines bearing sulfonamides. • Selective synthesis of isoxazolines using trichloroisocyanuric acid (TCCA) in EtOH-water as solvent. • Good to excellent yields and shorter reaction times under sonication. • Compound 3 h displayed promising cytotoxic activities against K562 and HL-60 cells., In the present study, following a one-pot two-step protocol, we have synthesized novel sulfonamides-isoxazolines hybrids (3a-r) via a highly regioselective 1,3-dipolar cycloaddition. The present methodology capitalized on trichloroisocyanuric acid (TCCA) as a safe and ecological oxidant and chlorinating agent for the in-situ conversion of aldehydes to nitrile oxides in the presence of hydroxylamine hydrochloride, under ultrasound activation. These nitrile oxides could be engaged in 1,3-dipolar cycloaddition reactions with various alkene to afford the targeted sulfonamides-isoxazolines hybrids (3a-r). The latter were assessed for their antineoplastic activity against model leukemia cell lines (Chronic Myeloid Leukemia, K562 and Promyelocytic Leukemia, HL-60).

A potential new drug to treat SARS-CoV-2 infections and chloroquine analogue, 5-((1H-imidazol-1-yl)methyl)quinolin-8-ol (DD1) has been here synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR, ultraviolet-visible, ESI-MS and single-crystal X-ray diffraction. DD1 was optimized in gas phase, aqueous and DMSO solutions using hybrid B3LYP/6-311++G(d,p) method. Comparisons between experimental and theoretical infrared spectra, 1H and 13C NMR chemical shifts and electronic spectrum in DMSO solution evidence good concordances. Higher solvation energy was observed in aqueous solution than in DMSO, showing in aqueous solution a higher value than antiviral brincidofovir and chloroquine. on Bond orders, atomic charges and topological studies suggest that imidazole ring play a very important role in the properties of DD1. NBO and AIM analyses support the intra-molecular O15-H16•••N17 bonds of DD1 in the three media. Low gap value supports the higher reactivity of DD1 than chloroquine justified by the higher electrophilicity and low nucleophilicity. Complete vibrational assignments of DD1 in gas phase and aqueous solution are reported together with the scaled force constants. In addition, better intermolecular interactions were observed by Hirshfeld surface analysis. Finally, the molecular docking mechanism between DD1 ligand and COVID-19/6WCF and COVID-19/6Y84 receptors were studied to explore the binding modes of these compounds at the active sites. Molecular docking results have shown that the DD1 molecule can be considered as a potential agent against COVID-19/6Y84-6WCF receptors., Graphical abstract Image, graphical abstract

A green and efficient regioselective protocol was developed for the preparation of novel isoxazolines and isoxazoles of N-saccharin derivatives via the water-promoted cycloaddition reaction of nitrile oxides with alkenes and alkynes. It is noteworthy that KI/Oxone/water-promoted one-pot three-component reactions of aldehyde, hydroxylamine hydrochloride, and alkene or alkyne were observed to be very satisfactory. The synthesis of all adducts (4a-j/5a-j) has been carried out by this method with high to excellent yields (70-95%) at 25°C within 30 min, using ultrasonic probe. All the new compounds were thoroughly characterized by spectroscopic techniques and also 5b, 5c and 5f were structurally identified by single-crystal X-ray diffraction methods. X-ray crystallography structure analysis clearly supported the regioselectivity of the cycloaddition reaction.

In the present study, a series of thiazolidine-2,4-diones derivatives (3a–3e) and (4a–4e) were synthesized and characterized by 1H NMR, 13C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. In vitro biological investigations revealed that most of compounds were active against α-glucosidase with IC50 values in the range of 43.85 ± 1.06 to 380.10 ± 1.02 µM, and α-amylase with IC50 in the range of 18.19 ± 0.11 to 208.10 ± 1.80 µM. Some of the tested compounds were found to be more potent inhibitors than the clinical drug Acarbose (IC50glucosidase = 97.12 ± 0.35 µM and IC50amylase = 2.97 ± 0.004 μM). The lead compounds were evaluated for their acute toxicity on Swiss mice and found to be completely non-toxic with LD > 2000 mg/kg BW. Furthermore, the Structure–activity relationship (SAR) and the binding interactions of all compounds with the active site of α-glucosidase and α-amylase were confirmed through molecular docking and stabilizing energy calculations. This study has identified the inhibitory potential a new class of synthesized thiazolidine-2,4-diones in controlling both hyperglycemia and type 2 diabetes mellitus. Furthermore, the theoretical binding mode of the target molecules was evaluated by molecular docking studies against the 3D Crystal Structure of human pancreatic α-amylase (PDB ID: 1B2Y) and α-glucosidase (PDB ID: 3W37) Communicated by Ramaswamy H. Sarma

(E)-N'-(2,4-dichlorobenzylidene)-5-phenyl-1H-pyrazole-3-carbohydrazide (E-DPPC) has been synthesized and characterized by FT-IR, 1H-NMR, ESI-MS, and single-crystal X-ray diffraction. The structures and properties of this new pyrazole-3-carbohydrazide derivative were studied in gas phase and aqueous solution by using Functional hybrid B3LYP/6-311++G** calculations in gas phase and in aqueous solution to study. Two stable structures (C1 and C2) with similar energies were found in the PES. C2 evidence a higher dipole moment and a volume contraction in solution attributed to the presence of donors and acceptors H bonds. Besides, the changes in orientation and direction of dipole moment vector in solution are attributed to the hydration of E-DPPC with water molecules. The repulsion existent between the negative MK, Mulliken and NPA charges on the N12 and O15 atoms explain the diminishing of N12-C14-O15 angle from 123.77 ° in gas phase to 123.03 ° in solution. Nucleophilic sites are visibly observed on the acceptor H bonds groups (N10, O15 and N22 atoms) while on the N18-H21, N12-H13, C11-H23, C2-H3, C17-H20 bonds characteristics electrophilic sites were found, being the N18-H21 bond the most labile donor of H bond with the lowest MEP and bond order values. NBO calculations suggest that C2 is clearly most stable in solution than in gas phase. AIM studies show that C2 is stable in both media due to new H bonds formed. Harmonic force fields in both media were calculated together with the scaled force constants while the 102 vibration normal modes expected for C2 were completely assigned. The comparisons of experimental NMR and UV-visible spectra with the corresponding predicted evidence reasonable correlations. Docking results also displayed that E-DPPC possessed good binding profile against receptor molecule and interacted with core residues of target protein.

A rapid and green method for the synthesis of novel N-thiazolidine-2,4-dione isoxazoline derivatives 5 from N-allyl-5-arylidenethiazolidine-2,4-diones 3 as dipolarophiles with arylnitrile oxides via 1,3-dipolar cycloaddition reaction. The corresponding N-allyl substituted dipolarophiles were prepared by one-pot method from thiazolidine-2,4-dione with aldehydes using Knoevenagel condensation followed by N-allylation of thiazolidine-2,4-dione in NaOH aqueous solution under sonication. In addition, the isoxazoline derivatives 5 were synthesized by regioselective and chemoselective 1,3-dipolar cycloaddition using inexpensive and mild NaCl/Oxone/Na

A simple and green one-pot reaction has been proposed for the synthesis of novel 3,5-disubstituted isoxazole-sulfonates and -sulfonamides (5a-j) in water under ultrasound irradiation. The methodology is based on the use of safe and environmentally friendly reagents and allows, via in-situ 1,3-dipolar cycloaddition, an easy access to functionalized heterocycles with the creation of four new bonds (S O, C N, C O and C C). Comparison studies using classical magnetic stirring and ultrasound irradiation clearly showed that sonication promoted clean transformation, high yields (72–89%) and faster reactions (20–28 min). All the synthesized compounds were fully characterized by MS-ES, 1H NMR, 13C NMR spectroscopy and HPLC analysis.

The search for new effective and eco-friendly corrosion inhibitors seems to be a never-ending task for practical applications. Herein, the principal objective of this work is to investigate the corrosion inhibition effect of novel 1,2,3-triazolyl nucleosides namely, 2-(acetoxymethyl)-5-(3-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate (TBAc) and 2-(acetoxymethyl)-5-(3-((1-(naphthalen-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate (TNAc) for mild steel (MS) in HCl solution. Different amounts of TBAc and TNAc inhibitors were prepared in 1.0 mol/L HCl medium, and their inhibition effect was investigated via electrochemical measurements, X-ray photoelectron spectroscopy (XPS), quantum chemical calculations (DFT), and molecular dynamics (MD) modeling. Further, we have examined the effect of iodide ions on inhibition efficiency, and the obtained data were compared and discussed. Results showed that these green compounds exhibited high inhibition performances thanks to their excellent molecular and electronic properties. They indicated that TNAc and TBAc showed high corrosion inhibition efficiencies at 5x10-3 mol/L with 0.1 mmol/L of KI. The inhibition efficiency of TNAc and TBAc reached 85% and 79% at 5x10-3 mol/L, while it improved to 94% and 91% in the presence of KI, respectively. Electrochemical tests revealed that the studied molecules acted as mixed-type inhibitors and they had a significant effect on the polarization resistance of mild steel. Moreover, the surface morphology analysis was performed using a scanning electron microscope (SEM) and XPS. Besides, a systematic understanding of how these molecules are adsorbed on steel surface was theoretically investigated. Taken together, experimental and theoretical results suggested a significant role of molecular properties of studied derivatives along with intermediate species in promoting their adsorption behavior. A consistent association was found between electrochemical measurements and theoretical calculations.

To date, the corrosion of metal surfaces is one of challenging problems in the modern business (technology and industrial applications). So, corrosion control of metal at different stage of application is necessary. To avoid this problem, organic and inorganic corrosion inhibitors are widely used. For this purpose, the present study deals with the corrosion inhibition assessment of novel uridine- (Murmu et al., 2020; Dehghani et al., 2020; Li et al., 2020) [1,2,3]triazole nucleosides as green corrosion inhibitors, namely 2-(acetoxymethyl)-6-(4-((3-(3,4-diacetoxy-5-(acetoxymethyl)tetrahydrofuran-2-yl)-2,6-dioxo-3,6-dihydropyrimidin-1(2H)-yl)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (TPTAc) and 2-(acetoxymethyl)-5-(3-((1-(3,4-diacetoxy-5-(acetoxymethyl)tetrahydrofuran-2-yl)-1H-1,2,3-triazol-4-yl)methyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate (TPDAc). After synthesis and characterization procedure, the corrosion inhibition performances of these compounds against the corrosion of mild steel (MS) are studied using both experimental and theoretical exploration. The effect and inhibition action of these inhibitors on the electrochemical behavior of MS corrosion was evaluated experimentally via electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), and weight loss techniques. In addition, theoretical calculations are made to analyze adsorption properties and characteristics of synthesized molecules on MS surface. The results obtained from all electrochemical experiments confirmed that the inhibitors understudy exhibited high inhibition performances thanks to their adsorption capacity on MS surface. EIS data indicated that TPTAc is quite effective at 5 × 10−3 M than TPDAc at the same concentration. PDP results revealed that the studied molecules acted as mixed-type inhibitors and they had a strong influence on the protective layer formed. The corrosion rate (CR) values considerably fall down from 1.135 mg cm−2 h−1 to 0.090 and 0.158 mg cm−2 h−1 at 5 × 10−3 M of TPTAC and TPDAc, respectively. Moreover, the effect of KI ions was also evaluated, and the results suggest that the presence of iodide ions has significantly improved the inhibition performances (97% for TPTAc and 90% for TPDAc at 5 × 10−3 M). Also, the calculated values of Gibb's free energy ( Δ G ads 0 ) are −33.61 kJ/mol and −34.33 kJ/mol for TPTAC and TPDAc, respectively; lying between −21 and −40 kJ/mol, confirming both physisorption as well as chemisorption interactions. In addition, results indicated that the inhibition intensity of studied compounds was expected to happen by means of adsorption over the MS surface which obeys the Langmuir's adsorption isotherm. The surface characterizations confirmed previous findings and contributed additional evidence on the morphological changes of MS surface during corrosion. The anti-corrosive and adsorption properties of studied compounds were detailed by DFT and molecular dynamics (MD) simulations. The results of theoretical calculations demonstrate strong and consistent agreement with experimental outcomes.

A green and efficient synthesis of new sulfonamide-1,2,3-triazoles 5 in heterogeneous conditions has been developed. The procedure involved one-pot four-component tandem sulfonamidation/azidation/1,3-dipolar cycloaddition (1,3- DC ) reactions under a cooperative effect of ultrasound irradiation and Cu (II) supported on amorphous mesoporous silica [mSiO2-Cu (II)] catalysis at room temperature in aqueous medium. In addition, the 1,4-disubstituted 1,2,3-triazoles 5 were synthesized by regioselective and chemoselective methods to afford the pure products in excellent yields and short reaction times under ultrasonic irradiation. The supported catalyst has been prepared from copper (II) nitrate by simple method using ultrasound activation and characterized by X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) method and Barrett-Joyner-Halenda (BJH) method. Also, the catalyst is easily prepared, stable, efficient, selective, and reusable under ultrasonic conditions.

International audience; A new, straightforward and eco-compatible route to C-(hetero)aryl nucleosides is reported. This ribosylation process consists of a one-step FeCl 3 catalyzed Friedel-Crafts b-C-glycosydation reaction. This reaction occurs through an oxonium intermediate from readily available protected sugars leading to functionalized C-nucleosides with high stereocontrol. The expected new C-nucleosides were obtained in good yields within a short reaction time (10 min). Moreover, this approach is compatible with the use of a range of bulky (poly)aromatics such as naphthalene, anthracene and pyrene, which are not easily accessible via classical routes. These new C-aryl-nucleosides exhibit interesting photophysical properties, underling their potential use for further nucleic acid labelling.

The aim of this study was to determine the chemical composition (fatty acids, tocopherols, and sterols) and evaluate the oxidative stability of Moroccan pomegranate (Punica granatum L.) seed oil. The oil content of pomegranate seed was 22.63 g/100g of dry weight. The fatty acid composition showed a dominance of conjugated linolenic acids (CLnAs) (86.96 g/100g). The most dominant fatty acid was punicic acid (75.1 g/100g), followed by catalpic acid (6.7 g/100g) and linoleic acid with amounts of 4.11 g/100g. The seed oil only contained a low level of saturated fatty acids with palmitic (2.64 g/100g) and stearic acids (1.73 g/100g) as main saturated fatty acids. The sterol marker, β-sitosterol, accounted for 404.59 mg/100g of the total sterol content in the seed oil. Total tocopherol content in seed oil was 332.44 mg/100g. γ-tocopherol (190.47 mg/100g oil) is the major constituent, followed by α-tocopherol (74.62 mg/100g oil) and δ-tocopherol (53.3 mg/100g oil). The induction time calculated by the Rancimat accelerated method was found to be of 3.6 h at 120 °C. In terms of oil, pomegranate seed oil may be considered as a valuable source for new multipurpose products with industrial, cosmetic and pharmaceutical uses.

The c-Jun N-terminal kinase (JNK) family, which comprises JNK1, JNK2 and JNK3, belongs to the mitogen-activated protein kinase (MAPK) superfamily, whose members regulate myriad biological processes, including those implicated in tumorigenesis and neurodegenerative disorders. As with many other kinases, JNKs can adopt two main conformational changes: the DFG-in (active) conformation and the DFG-out (inactive) conformation; however, to date, the only resolved DFG-out conformation is that of JNK2. Structural elucidation of the remaining DFG-out conformations will be critical for structure-based drug design of novel type II inhibitors, which have been shown to offer greater therapeutic benefit than do type I inhibitors, as demonstrated by imatinib in chronic myeloid leukemia. Herein we report the use of a homology-modeling approach to build models of the DFG-out conformations of JNK1 and JNK3. After validating the model structures, we used structure-based drug design to elucidate the principal structural differences among the three JNK active sites and the binding of known JNK inhibitor, and to explain the selectivity of this compound for JNK2. Our findings provide structural guidelines for the design of novel and selective type II JNK inhibitors.

The anti-corrosion potency of three synthesized 8-hydroxyquinoline derivatives, namely 5-(azidomethyl)-7-(morpholinomethyl)quinolin-8-ol (HM1), 2-(8-hydroxy-7-(morpholinomethyl)quinolin-5-yl)acetonitrile (HM2), 5-(azidomethyl)-7-(piperidin-1-ylmethyl)quinolin-8-ol (HM3) in hydrochloric acid for mild steel was investigated using weight loss and electrochemical techniques. Potentiodynamic polarization (PDP) data reveal that all three compounds were cathodic inhibitors, with HM3 presentation significant mixed-type effect at high inhibitor concentrations (10−3 M). Electrochemical impedance spectroscopy (EIS) data reveal better adsorption of compounds species on MS surface at increased inhibitor concentrations with HM1, HM2 and HM3 reaching a maximum efficiency of 90, 89 and 88%. The three compounds HM1, HM2 and HM3 were inclined towards the Langmuir adsorption-isotherm by spontaneous chemical-physical adsorptions of inhibitors on the mild steel surface. The correlation between the electronic properties and inhibition efficacies of the tilted inhibitors was determined by using simple linear regression technique. Electronic properties were calculated for neutral and protonated forms in a polarizable continuum model using the DFT method at the B3LYP/6–311 + G (d, p) level of theory. The active adsorbed sites of HM1-HM3 on the metal surface were determined by analyzing their corresponding electrostatic surface potentials (ESP). Furthermore, molecular dynamics simulations have been performed to illustrate the most conceivable adsorption configuration between the inhibitors and metal surface.

We report herein a simple and efficient synthesis of a new series of antibacterial uridine nucleosides. The strategy involved a sequential silylation/N-glycosylation/N-propargylation procedure of uracil 1 for preparing the dipolarophile 5 in good yield. A series of novel uridine-[1,2,3]triazole nucleosides 6a-j were efficiently synthesized via the copper-catalyzed azide-alkyne cycloaddition (CuAAC) from dipolarophile 5 with different selected azides. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvements were observed when reactions were carried out under sonication. Their antibacterial potential has been evaluated by means of a micro-dilution assay against either Gram-positive or Gram-negative bacteria. Compounds 6i and 6j have shown significant bactericidal activity against Staphylococcus aureus (MIC = 10 and 6 μM, respectively), and 6h against Escherichia coli (MIC = 8 μM). Moreover, antibacterial kinetic assays showed that 6i and 6j significantly reduced the S. aureus growth rate at the MIC concentration, after 6 h, compared to their deprotected analogs, 6k and 6l, respectively. Compound 6h also significantly reduced the growth of E. coli. These antibacterial effects may be related to the penetrating properties of these compounds, as revealed by the leakage of nucleic acids from the sensitive strains.

The C-aryl-ribosyles are of utmost interest for the development of antiviral and anticancer agents. Even if several synthetic pathways have been disclosed for the preparation of these nucleosides, a direct, few steps and modular approaches are still lacking. In line with our previous efforts, we report herein a one step - eco-friendly β-ribosylation of aryles and heteroaryles through a direct Friedel-Craft ribosylation mediated by bismuth triflate, Bi(OTf)3. The resulting carbohydrates have been functionalized by cross-coupling reactions, leading to a series of new C-aryl-nucleosides (32 compounds). Among them, we observed that 5d exerts promising anti-proliferative effects against two human Chronic Myeloid Leukemia (CML) cell lines, both sensitive (K562-S) or resistant (K562-R) to imatinib, the “gold standard of care” used in this pathology. Moreover, we demonstrated that 5d kills CML cells by a non-conventional mechanism of cell death.

An inexpensive, simple and highly efficient process was developed for the selective anomeric azidation of protected sugars using a cooperative effect of iron catalysis and ultrasound activation, in the presence of SO2(N3)2. The latter, as a soluble azide source, is generated in situ by reaction of sodium azide with sulfuryl chloride under sonication. The obtained azidoglycosides undergo clean 1,3-dipolar cycloaddition with terminal alkynes under ultrasound activation to afford 1,2,3-triazole glycosides in high yields. These results illustrate that ultrasounds can significantly enhance the efficiency of both azidation and cycloaddition steps and lead to good overall yields. The stereo- and regioselectivities of the azidation and the 1,3-dipolar cycloaddition reactions have also been examined.

Phenol derived O-glycosides were synthesized using a direct and convenient O-glycosidation, starting from acetylated sugars in the presence of FeCl3, an inexpensive, mild and benign Lewis acid catalyst. The reactions were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement in rates and yields were observed when reactions were carried out under sonication compared with conventional conditions leading to the corresponding β-O-glycosides as the major anomer. Post-synthetic transformations of iodophenol intermediates led to new resveratrol O-glycoside analogs in good overall yields.

International audience; A series of nucleoside analogues bearing a 1,4,5-trisubstituted-1,2,3-triazole aglycone was synthesized using a straightforward click/electrophilic addition or click/oxidative coupling tandem procedures. SAR analysis, using cell culture assays, led to the discovery of a series of compounds belonging to the 5-alkynyl-1,2,3-triazole family that exhibits potent antileukemic effects on several hematologic malignancies including chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) either sensitive or resistant to their respective therapy. Compound 4a also proved efficient in vivo on mice xenografted with SKM1-R MDS cell line. Additionally, some insights in its mode of action revealed that this compound induced cell death by caspase and autophagy induction.

A series of novel 3,5-disubstituted isoxazoles have been synthesized, using a new, green, and versatile "one-pot three-steps" methodology. The key step is an oxidative 1,3-dipolar cycloaddition under ultrasonic irradiation, occurring in aqueous media, and mediated by cerium (IV) ammonium nitrate (CAN). CAN is a one-electron oxidant, highly soluble in water, slightly toxic and inexpensive, that allows the in situ conversion of the intermediate aldoximes into nitrile oxide. The syntheses are highly regioselective, as illustrated by the structures of the final compounds, which have been fully assessed by spectral analyses (1H and 13C NMR, MS). This study illustrates the potency of the ultrasound activation to synthesize a set of highly functionalized heterocycles, with potential applications in biology, in short reaction times and following an eco-friendly process.

International audience; Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market. To improve the activity of AICAR, we report herein an efficient synthesis of new series of sulfonamide-4-substituted-1,2,3-triazolyl nucleosides using a Cu-catalyzed 1,3-dipolar cycloaddition. All these molecules have been fully characterized and evaluated against two aggressive tumor cell lines, RCC4 and MDA-MB-231. Among them, nucleoside analogue 5i belonging to the ribose series was found to be 19 to 66-fold more active than AICAR. Western blot analyses on RCC4 cells showed that 5i displayed an interesting mode of action by inducing both apoptosis and autophagy cell death, making therefore this class of molecules highly promising for further hit-to-lead optimization.

Novel isoxazoline and pyrazoline derivatives of N-substituted saccharin were synthesized in good yields by 1,3-dipolar cycloaddition of N-crotonoyl- or N-cinnamoylsaccharin as dipolarophile to arylnitrile oxides or nitrile imines using p-HAP300 as catalyst under solventfree microwave conditions. In this process, the yields were significantly improved compared to classical conditions without alteration of the selectivity. The regioselectivity as well as the nonthermal specific microwave effect are discussed.

In the title compound, C15H15NO5S, the benzene and heterocyclic rings are close to being coplanar [dihedral angle = 1.49 (6)°]. In the crystal, pairwise C—H...O hydrogen bonds form dimers, which are arranged into `stair-step' rows by way of C=O–π interactions between a carbonyl group and the benzene ring [O...π = 3.3837 (12) Å].

Novel isoxazoline and pyrazoline derivatives of N-substituted saccharin were synthesized in good yields by 1,3-dipolar cycloaddition of N-crotonoyl- or N-cinnamoylsaccharin as dipolarophile to arylnitrile oxides or nitrile imines using p-HAP300 as catalyst under solvent-free microwave conditions. In this process, the yields were significantly improved compared to classical conditions without alteration of the selectivity. The regioselectivity as well as the nonthermal specific microwave effect are discussed., This work was funded by grants from the CNRSTMorocco “Centre National de la Recherche Scientifique et Technique” and the University Mohammed V of Rabat. It was also supported by Egide PHC Toubkal (30330ZF, MA/14/304), CNRS-France “Centre National de la Recherche Scientifique” and UNSA “University Nice-Sophia Antipolis”. The authors would like to thank UATRS “Unités d’Appui Technique à la Recherche Scientifique” – CNRST for spectral analysis.

A sustainable Knoevenagel condensation of a series of aldehydes with malononitrile and ethyl cyanoacetate is described. The process is based on the combination of microwave activation and hydroxyapatite catalysis under solvent-free conditions. Products are obtained in and high yields after short reaction times. The effects of the specific surface of porous calcium hydroxyapatite and microwave activation are discussed.