Synthesis of C8-glycomimetics as potential glycosidases inhibitors

The synthesis of C8-glycomimetics is described from C₂-symmetrical polyhydroxylated cyclooctenes derived from carbocyclisation of enantiomerically pure 1,9-dienes by ring closing metathesis. Their obtention notably involved either hydroboration followed by oxidation to carbasugars or to cyclooctanones then reductive amination, or formation of a cis-cyclic sulfate followed by successive introduction of an azido group, reduction and subsequent reductive amination. The biological activity of the C8-carbasugars and related aminocyclitols, analogous to voglibose, has been evaluated towards several commercially available glycosidases.     

Efficient synthesis in three steps and spectral determination of methyl‐5‐[(o‐, m‐, and p‐substituted‐phenylthio]‐2‐benzimidazolecarbamates

The preparation and spectral properties often novel methyl 5‐[(o‐, m‐, and p‐substituted)‐phenylthio]‐2‐benzimidazolecarbamates with possible pharmacological activity as antihelmintics is described; by condensation and cyclization between 5‐methylthioures sulfate chloroformic acid methyl ester and 3,4‐diaminophenyl‐substituted‐phenylthio ether dissolved in ethanol. The structures of all final products were corroborated by ir; ¹H‐nmr, ¹³C‐nmr and ms.     

Efficient synthesis and spectral determination of 11‐[(o‐ m‐ and p‐substituted)‐phenyl]‐8‐chloro‐3,3‐dimethyl‐2,3,4,5,10,11‐hexahydro‐1H‐dibenzo[b,e][1,4]diazepin‐1‐ones

A new synthesis to obtain eleven novel derivatives of 11‐[(o‐ m‐ and p‐substituted)‐phenyl]‐8‐chloro‐3,3‐dimethyl‐2,3,4,5,10,11‐hexahydro‐1H‐dibenzo[b,e][1,4]diazepin‐1‐ones with possible pharmacological activity in the central nervous system in two efficient steps has been developed. The final products were obtained by condensation and cyclization between 3‐[4‐chloro‐1,2‐phenylenediamine]‐5,5‐dimethyl‐2‐cyclohexenone with (o‐ m‐ and p‐substituted)benzaldehyde. The structure of all products was corroborated by ir, ¹H‐nmr, ¹³C‐nmr and high resolution in ms.     

Synthesis and spectral properties of 7‐chloro‐5‐[(o‐ and p‐R1)phenyl]‐1‐R2‐3H‐[1,4]benzodiazepin‐2‐ones

A series of twelve new 7‐chloro‐5‐[(o‐ and p‐R₁)phenyl]‐1‐R₂‐3H‐[1,4] benzo‐diazepin‐2‐ones, which have possible pharmacological properties were synthesized. The synthesis of all the final compounds was carried out by four steps. The structure of all final products was corroborated by ir, ¹H nmr, ¹³C nmr and ms, and have been obtained in 35‐94% yield.     

A Water Molecule Triggers Guest Exchange at a Mono-Zinc Centre Confined in a Biomimetic Calixarene Pocket: a Model for Understanding Ligand Stability in Zn Proteins

In this study, the ligand exchange mechanism at a biomimetic Zn^II centre, embedded in a pocket mimicking the possible constrains induced by a proteic structure, is explored. The residence time of different guest ligands (dimethylformamide, acetonitrile and ethanol) inside the cavity of a calix[6]arene-based tris(imidazole) tetrahedral zinc complex was probed using 1D EXchange SpectroscopY NMR experiments. A strong dependence of residence time on water content was observed with no exchange occurring under anhydrous conditions, even in the presence of a large excess of guest ligand. These results advocate for an associative exchange mechanism involving the transient exo-coordination of a water molecule, giving rise to 5-coordinate Zn^II intermediates, and inversion of the pyramid at the Zn^II centre. Theoretical modelling by DFT confirmed that the associative mechanism is at stake. These results are particularly relevant in the context of the understanding of kinetic stability/lability in Zn proteins and highlight the key role that a single water molecule can play in catalysing ligand exchange and controlling the lability of Zn^II in proteins.     

Helical supramolecular assembly of N2,N2′‐bis[3‐(morpholin‐4‐yl)propyl]‐N1,N1′‐(1,2‐phenylene)dioxalamide dimethyl sulfoxide monosolvate

In the title compound, C₂₄H₃₆N₆O₆·C₂H₆OS, the carbonyl groups are in an antiperiplanar conformation, with O=C—C=O torsion angles of 178.59 (15) and −172.08 (16)°. An intramolecular hydrogen‐bonding pattern is depicted by four N—H...O interactions, which form two adjacent S(5)S(5) motifs, and an N—H...N interaction, which forms an S(6) ring motif. Intermolecular N—H...O hydrogen bonding and C—H...O soft interactions allow the formation of a meso‐helix. The title compound is the first example of a helical 1,2‐phenylenedioxalamide. The oxalamide traps one molecule of dimethyl sulfoxide through N—H...O hydrogen bonding. C—H...O soft interactions give rise to the two‐dimensional structure.     

Guest Covalent Capture by a Host: A Biomimetic Strategy for the Selective Functionalization of a Cavity

A biomimetic strategy for the monofunctionalization of a calix[6]arene core is described. It is based on host–guest chemistry (mimicking the Michaelis–Menten adduct in enzymes) and allows the finely tuned pre‐organization of the substrate (an alkyne) with respect to the reactant (three azido groups introduced at the calixarene large rim). It is shown that the thermal Huisgen reaction implemented in this work proceeds under very mild conditions with total regioselectivity of the cycloaddition process. The scope of the reaction was explored and the results suggest that such a supramolecular strategy is quite versatile and could be applied to the selective functionalization of other cavitands bearing different recognition patterns. A detailed structural, thermodynamic, and kinetic study is also reported, highlighting interesting biomimetic features: The importance of the host–guest adduct strength, the high sensitivity of the reaction to the pre‐organization of the reactive partners (alkyne vs. azide), and a significant impact of the embedment on the transition state. The self‐coordination of the monofunctionalized products was also studied and an “endo/exo” switch of the internal side‐chain could be triggered by adding competitive ligands.     

Green Synthesis and Applications of ZnO and TiO2 Nanostructures

Over the last two decades, oxide nanostructures have been continuously evaluated and used in many technological applications. The advancement of the controlled synthesis approach to design desired morphology is a fundamental key to the discipline of material science and nanotechnology. These nanostructures can be prepared via different physical and chemical methods; however, a green and ecofriendly synthesis approach is a promising way to produce these nanostructures with desired properties with less risk of hazardous chemicals. In this regard, ZnO and TiO₂ nanostructures are prominent candidates for various applications. Moreover, they are more efficient, non-toxic, and cost-effective. This review mainly focuses on the recent state-of-the-art advancements in the green synthesis approach for ZnO and TiO₂ nanostructures and their applications. The first section summarizes the green synthesis approach to synthesize ZnO and TiO₂ nanostructures via different routes such as solvothermal, hydrothermal, co-precipitation, and sol-gel using biological systems that are based on the principles of green chemistry. The second section demonstrates the application of ZnO and TiO₂ nanostructures. The review also discusses the problems and future perspectives of green synthesis methods and the related issues posed and overlooked by the scientific community on the green approach to nanostructure oxides.     

Synthesis,Antiprotozoal Activity,and Cheminformatic Analysis of 2-Phenyl-2H-Indazole Derivatives

Indazole is an important scaffold in medicinal chemistry. At present, the progress on synthetic methodologies has allowed the preparation of several new indazole derivatives with interesting pharmacological properties. Particularly, the antiprotozoal activity of indazole derivatives have been recently reported. Herein, a series of 22 indazole derivatives was synthesized and studied as antiprotozoals. The 2-phenyl-2H-indazole scaffold was accessed by a one-pot procedure, which includes a combination of ultrasound synthesis under neat conditions as well as Cadogan’s cyclization. Moreover, some compounds were derivatized to have an appropriate set to provide structure-activity relationships (SAR) information. Whereas the antiprotozoal activity of six of these compounds against E. histolytica, G. intestinalis, and T. vaginalis had been previously reported, the activity of the additional 16 compounds was evaluated against these same protozoa. The biological assays revealed structural features that favor the antiprotozoal activity against the three protozoans tested, e.g., electron withdrawing groups at the 2-phenyl ring. It is important to mention that the indazole derivatives possess strong antiprotozoal activity and are also characterized by a continuous SAR.     

In Vitro Antiplasmodial and Cytotoxic Activities of Compounds from the Roots of Eriosema montanum Baker f. (Fabaceae)

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC₅₀ (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC₅₀ (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots’ crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria.