Efficacious One-pot Synthesis of 2-thiazolines and 2-oxazolines Under Solvent and Metal-Free Conditions

International audienceBackground: 2-oxazolines and 2-thiazolines are important heterocycles due to their extensive applications in chemistry, biochemistry, and pharmacology. Most of the precedent methods for preparing these heterocycles involve one or more drawbacks, including harsh reaction conditions, long reaction times, low yields of products, high temperature, and toxic solvents. Objective: The aim of this study was to develop a new and eco-efficient method for the preparation of 2-oxazolines and 2-thiazolines. Methods: Amino alcohols were condensed with nitriles in a sealed tube under solvent-free and metal- free conditions. Results: Our procedure appears to be highly eco-efficient and promotes quantitative access to 2-oxazolines and 2-thiazolines using simple and minimum manipulation. Conclusion: This simple approach allows high conversion for different nitriles yielded from 78 to 99% and easy isolation of the targeted products without further purification. To the best of our knowledge, our procedure is the most efficient and fast method reported to date in terms of chemical yields, number of steps, and atom economy

Merging Grubbs second-generation catalyst with photocatalysis enables <i>Z</i>-selective metathesis of olefins: scope, limitations, and mechanism

International audienceOlefin cross-metathesis is a cornerstone reaction in organic synthesis where stereoselectivity is typically governed by the structure of the catalyst. In this work, we show that merging Grubbs second generation catalyst, a classical E-selective catalyst, with a readily available photocatalyst, enables the exclusive formation of the contra-thermodynamic Z-isomer. The scope and limitations of this unprecedented approach are discussed based on both computational and experimental mechanistic data

Potential of Citrullus colocynthis L. Schrad. Immature Seed Extracts as Food Preservative against a Fungal Mycotoxigenic Contaminant

'e world of plant extracts and natural compounds have long been regarded as a promise land for the individuation of healthyalternatives to chemical preservatives, against microbial contamination, in food and feed commodities. A plethora of aromatic andmedicinal plant species have been studied from decades to explore their antimicrobial and antioxidant properties, in order to bothvalidate their ethnobotanical use for healing microbial illnesses and assess their suitability as food preservation agents. In fact, afterterrestrialization and during the following evolutionary pathway, plants had to develop chemical compounds—constitutive and/or induced—for defence against specific pathogens, therefore becoming a potential source of new natural products usable withantimicrobial purposes. Aside from the most common contaminants that could occur in foodstuff, mycotoxigenic fungal speciesrepresent a big concern, mainly in cereals and derived products: aflatoxins in particular are the most dreaded among such toxicand cancerogenic secondary metabolites, and the control of the main producerAspergillus flavusis currently one of the mostpursued goals in the field of food safety. As aromatic and medicinal plants have a long history of use in the Mediterranean basin forboth food preservation and pest control in crops, the exploitation of native species for the control of mycotoxigenic phyto-pathogens is almost rationale. 'e present work provides novel insights into the possible use ofC. colocynthisseed organic extractsas antimycotoxigenic additives, demonstrating, for some of them, a feasible application as crop and food protectants with specificregard to aflatoxin contamination. Additionally, the evaluation of their cytotoxic potential and nitric oxide production on humancell lines has been reported for the first tim

Optimized Extraction, Preliminary Characterization and Evaluation of the in Vitro Anticancer Activity of Phlorotannin-Rich Fraction from the Brown Seaweed, Cystoseira sedoides

International audienceBrown seaweeds produce useful bioactive substances with high cosmetic and pharmacological values due to the presence of antioxidant derivatives, mainly phlorotannins (PHT), which are of particular interest. A central composite rotatable design (CCRD) with three variables (extraction time, dry material-to-solvent ratio and ethanol concentration) and two responses was performed to optimize the microwave-assisted extraction (MAE) of phlorotannins from Cystoseira sedoides using response surface methodology (RSM). Results showed that the independent variables significantly affected both phlorotannin content and the scavenging capacity. The optimum operating conditions were extraction time, 101.74 sec; dry material-to-solvent ratio, 1:10 g/mL; and ethanol extraction, 50%. Under these conditions, the predicted values of PHT content and radical scavenging activity-IC50 were close to the observed values and were 383.887 mu g PGE/g Dm and 18.353 mu g/mL, respectively. Characterization of the phlorotannin-rich fraction was conducted by high-performance liquid chromatography and Fourier transform infrared spectroscopy. The evaluation of the anticancer activity against MCF-7 breast cancer cell line showed a potent activity to trigger apoptotic death in more than a half of the MCF-7 cells, with an estimated IC50 value of 78 mu g/mL. In addition, this fraction induced a notable growth regression effect on 3D spheroids model in a concentration-dependent manner, with a growth rate of about 1.17, at 200 mu g/mL

Structure-activity relationship study of hypoxia-activated prodrugs for proteoglycan-targeted chemotherapy in chondrosarcoma

International audienceDue to an abundant chondrogenic, poorly vascularized and particularly hypoxic extracellular matrix, chondrosarcoma, a malignant cartilaginous tumour, is chemo- and radio-resistant. Surgical resection with wide margins remains the mainstay of treatment. To address the lack of therapy, our strategy aims to increase anticancer drugs targeting and delivery in the tumour, by leveraging specific chondrosarcoma hallmarks: an extensive cartilaginous extracellular matrix, namely the high negative fixed charge density and severe chronic hypoxia. A dual targeted therapy for chondrosarcoma was investigated by conjugation of a hypoxia-activated prodrug (HAP) to quaternary ammonium (QA) functions which exhibit a high affinity for polyanionic sites of proteoglycans (PGs), the major components of the chondrosarcoma extracellular matrix. Based on preclinical results, an imidazole prodrug, ICF05016, was identified and provided the basis for a lead optimization study. A series of 27 QA-phosphoramide mustard conjugates, differing by the type of QA function and the length of the alkyl linker, was yielded by a common multi-step sequence involving phosphorylation of a key 2-nitroimidazole alcohol. Then, a screening was realized by surface plasmon resonance technology to assess biomolecular interactions between QA derivatives and aggrecan, the most abundant PG in chondrosarcoma. Results revealed that affinity depends more on the type of QA function, than on the linker length. Moreover, the presence of a benzyl group enhanced affinity to aggrecan. Twelve compounds were shortlisted and evaluated for antiproliferative activity (i.e., growth inhibiting concentration 50), under normoxic and hypoxic conditions using the human extraskeletal myeloid chondrosarcoma cell line (HEMC-SS). For all prodrugs, hypoxic selectivity was maintained and even increased, compared with the lead. From this study, compound 31f emerged as the most effective PG-targeted HAPs with a dissociation constant of 2.10 μM in the SPR experiment, a hypoxia cytotoxicity ratio of 24 and an efficient reductive cleavage under chemical and enzymatic conditions

Antioxidant, Anticancer, Antibacterial, Antibiofilm Properties and Gas Chromatography and Mass Spectrometry Analysis of Manuka Honey: A Nature’s Bioactive Honey

Honey has a history of medical use and is known as bio-alternative therapy. This research assessed the phytochemical and biological activity of the medical grade manuka honey (MH). Gas chromatography–mass spectrometry (GC–MS) was chosen to investigate bioactive compounds of the MH. The DPPH and ABTS free radical scavenging and beta-carotene antioxidant activities as well as the antibacterial and antibiofilm effects against S. aureus, B. subtilis, E. coli and P. aeruginosa were all determined. Furthermore, to gauge anticancer properties of MH, a MTT assay was opted towards three cell lines, including HCT-116 (colon), A549 (lung) and MCF-7 (breast) cancer cells. The GC–MS analysis of the tested MH revealed the identification of various chemical constituents belonging to the fatty acids, phenols, and esters. The MH was found to have higher reducing power activity (DPPH IC50: 7.36; ABTS IC50: 4.49 mg/mL) than the beta-carotene bleaching power (IC50: 37.51 mg/mL). Similarly, the MH was noted to be more active against the planktonic and biofilm of Gram-positive bacteria. Furthermore, a dose-dependent anticancer potential was observed, although a significant anticancer potential was pointed out against the MCF-7 and A549 cell conforming to the IC50 values of 9.05 and 9.37 mg/mL, respectively. This study’s results have highlighted the MH’s chemical composition with significant bioactivities