Interaction between carbon dots from folic acid and their cellular receptor: a qualitative physicochemical approach.

According to the World Health Organization, the number of cancers (all cancers, both sexes, all ages and worldwide) in 2020 reached a total of 19 292 789 new cases leading to 9 958 133 deaths during the same period. Many cancers could be cured if detected early. Preventing cancer and detecting it early are two essential strategies for controlling this pathology. For this purpose, several strategies have been described for imaging cancer cells. One of them is based on the use of carbon nanoparticles called carbon dots, tools of physical chemistry. The literature describes that cancer cells can be imaged using carbon dots obtained from folic acid and that the in cellulo observed photoluminescence probably results from the interaction of these nanoparticles with the folic acid-receptor, a cell surface protein overexpressed in many malignant cells. However, this interaction has never been directly demonstrated yet. We investigated it, for the first time, using (i) freshly synthesized and fully characterized carbon dots, (ii) folate binding protein, a folic acid-receptor model protein and (iii) fluorescence spectroscopy and isothermal titration calorimetry, two powerful methods for detecting molecular interactions. Our results even highlight a selective interaction between these carbon made nano-objects and their biological target.

Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis.

Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC50) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.

Application of multivariate linear regression models for selection of deep eutectic solvent for extraction of apigenin and luteolin from Chrysanthemum indicum L.

INTRODUCTION: Among a variety of compounds presented in chrysanthemum, apigenin and luteolin are the two main components that play a major role in numerous biological activities of this herb. OBJECTIVES: We aimed to obtain linear models showing the dependence of the yield of extraction of apigenin and luteolin on the composition of deep eutectic solvent and investigate the extraction of these two ingredients from Chrysanthemum indicum L. METHODS: Two models showing the dependence of luteolin and apigenin concentrations on the composition of the solvent were established using a multilinear regression algorithm and were applied to screen 119 different solvents. After that, the extraction process was optimized using response surface methodology and an artificial neural network. Apigenin and luteolin were recovered from the extract by the combination of distillation and addition of water. RESULTS: The screening results on 119 solvents revealed that choline chloride-acetic acid (1:4) was the most suitable deep eutectic solvent. It was showed that both response surface methodology and the artificial neural network could accurately determine the optimal conditions of extraction of apigenin and luteolin from C. indicum L., including time of extraction (65 minutes), temperature of extraction (90°C) and water content (20%). By the combination of distillation and addition of water, apigenin and luteolin could be effectively recovered from the deep eutectic solvent extract with a recovery rate of over 80%. CONCLUSIONS: Deep eutectic solvent could be used as an effective green alternative to the conventional solvents for the extraction of bioactive compounds from plants.

Inhibitory Effects of Secondary Metabolites from the Lichen Stereocaulon evolutum on Protein Tyrosine Phosphatase 1B.

Protein tyrosine phosphatase 1B plays a significant role in type 2 diabetes mellitus and other diseases and is therefore considered a new drug target. Within this study, an acetone extract from the lichen Stereocaulon evolutum was identified to possess strong protein tyrosine phosphatase 1B inhibition in a cell-free assay (IC50 of 11.8 µg/mL). Fractionation of this bioactive extract led to the isolation of seven known molecules belonging to the depsidones and the related diphenylethers and one new natural product, i.e., 3-butyl-3,7-dihydroxy-5-methoxy-1(3H)-isobenzofurane. The isolated compounds were evaluated for their inhibition of protein tyrosine phosphatase 1B. Two depsidones, lobaric acid and norlobaric acid, and the diphenylether anhydrosakisacaulon A potently inhibited protein tyrosine phosphatase 1B with IC50 values of 12.9, 15.1, and 16.1 µM, respectively, which is in the range of the protein tyrosine phosphatase 1B inhibitory activity of the positive control ursolic acid (IC50 of 14.4 µM). Molecular simulations performed on the eight compounds showed that i) a contact between the molecule and the four main regions of the protein is required for inhibitory activity, ii) the relative rigidity of the depsidones lobaric acid and norlobaric acid and the reactivity related to hydrogen bond donors or acceptors, which interact with protein tyrosine phosphatase 1B key amino acids, are involved in the bioactivity on protein tyrosine phosphatase 1B, iii) the cycle opening observed for diphenylethers decreased the inhibition, except for anhydrosakisacaulon A where its double bond on C-8 offsets this loss of activity, iv) the function present at C-8 is a determinant for the inhibitory effect on protein tyrosine phosphatase 1B, and v) the more hydrogen bonds with Arg221 there are, the more anchorage is favored.

In vitro activities of a new fluoroquinolone derivative highly active against Chlamydia trachomatis.

Chlamydia trachomatis is a bacterial human pathogen responsible for the development of trachoma, an infection leading to blindness, and is also the cause of the main bacterial sexually transmitted infection worldwide. We designed a new inhibitor of this bacterium with, however, some prerequisites using (i) the iron dependency of the bacterium, (ii) a commercially available broad-spectrum antibiotic and (iii) a short synthetic pathway. The corresponding 8-hydroxyquinoline-ciprofloxacin conjugate was evaluated against a panel of pathogenic bacteria, including C. trachomatis but also the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species). Its anti-Chlamydia activity is higher than that of ciprofloxacin and seems to be related to the fluoroquinolone moiety of the molecule, which is also responsible for the complexation of iron(III), as demonstrated by spectrophotometric titration.

Inhibition of Chlamydia trachomatis Growth During the Last Decade: A Mini-Review.

Chlamydia trachomatis is responsible for the most frequent sexually transmitted bacterial infection in the world and for trachoma, the world's leading infectious cause of blindness. Genital chlamydial infection is very common among sexually active young people, and when untreated, leads to serious complications. No vaccine is yet available for this bacterial infection. Although Chlamydia resistance to antibiotics is rarely observed in vivo, studies showed that 10-20% of patients remain infected at the end of antibiotherapy, without being reinfected. The present review gives a global and comprehensive overview of the different targets and the related inhibitors proposed during the last decade, with a view to limiting the growth of this human pathogen. Metallic and polymeric nanoparticles in this field are also briefly presented.

Evolution and Spatiotemporal Dynamics of Enterovirus A71 Subgenogroups in Vietnam.

Background: Enterovirus A71 (EV-A71) is the major cause of severe hand, foot, and mouth disease and viral encephalitis in children across the Asia-Pacific region, including in Vietnam, which has experienced a high burden of disease in recent years. Multiple subgenogroups (C1, C4, C5, and B5) concurrently circulate in the region with a large variation in epidemic severity. The relative differences in their evolution and epidemiology were examined within Vietnam and globally. Methods: A total of 752 VP1 gene sequences were analyzed (413 generated in this study combined with 339 obtained from GenBank), collected from patients in 36 provinces in Vietnam during 2003-2013, along with epidemiological metadata. Globally representative VP1 gene datasets of subgenogroups were used to coestimate time-resolved phylogenies and relative genetic diversity to infer virus origins and regional transmission network. Results: Despite frequent virus migration between countries, the highest genetic diversity of individual subgenogroups was maintained independently for several years in specific Asian countries representing genogroup-specific sources of EV-A71 diversity. Conclusion: This study highlights a persistent transmission network of EV-A71, with specific Asian countries seeding other countries in the region and beyond, emphasizing the need for improved EV-A71 surveillance and detailed genetic and antigenic characterization.

Depsides: lichen metabolites active against hepatitis C virus.

A thorough phytochemical study of Stereocaulon evolutum was conducted, for the isolation of structurally related atranorin derivatives. Indeed, pilot experiments suggested that atranorin (1), the main metabolite of this lichen, would interfere with the lifecycle of hepatitis C virus (HCV). Eight compounds, including one reported for the first time (2), were isolated and characterized. Two analogs (5, 6) were also synthesized, to enlarge the panel of atranorin-related structures. Most of these compounds were active against HCV, with a half-maximal inhibitory concentration of about 10 to 70 µM, with depsides more potent than monoaromatic phenols. The most effective inhibitors (1, 5 and 6) were then added at different steps of the HCV lifecycle. Interestingly, atranorin (1), bearing an aldehyde function at C-3, inhibited only viral entry, whereas the synthetic compounds 5 and 6, bearing a hydroxymethyl and a methyl function, respectively, at C-3 interfered with viral replication.