116 research outputs found
Study about an anti-inflammatory natural diterpenes family
No full textAndrographis paniculata est une échinacée d’origine asiatique utilisée depuis plus de deux milles ans en médecine traditionnelle asiatique. Ses activités anti-bactériennes, anti-virales et hépatoprotectrices, entre autre, en ont fait un sujet d’étude important depuis les trente dernières années. Cette plante est principalement constituée de diterpènes de série ent-labdanes, dont le composé majoritaire est l’andrographolide, une lactone diterpénique, qui a montré des propriétés anti-inflammatoires sur la voie NFB. C’est dans le but de comprendre et d’améliorer les activités anti-inflammatoires des composés issus de la plante que nous avons envisagé l’étude de la famille des andrographolides. Une étude qualitative d’extraits issus de compléments alimentaires a permis d’obtenir trois composés naturels, qui ont été pharmacomodulés chimiquement. De plus, une méthode quantitative de quatre extraits bruts a permis de déterminer la concentration des trois composés naturels isolés dans chaque mélange. Les composés isolés, ceux modifés par hémisynthèse, ainsi que les mélanges de composition déterminée ont fait l’objet de tests d’activité anti-inflammatoire. Afin de modifier la structure de l’andrographolide sur des positions non accessibles par hémisynthèse, la synthèse totale et énantiosélective du produit naturel a été envisagée. Deux voies de synthèses ont été envisagées pour la préparation de ce composé : une voie biomimétique et une voie utilisant la cétone de Wieland-Miescher. Cette dernière voie est divisée en trois parties (cyclisation énantiosélective, fonctionnalisation du cycle A, fonctionnalisation du cycle B). Ainsi, nous avons pu mettre au point des méthodologies permettant de fonctionnaliser chaque cycle et d’accéder à la synthèse d’analogues de l’andrographolide.Andrographis paniculata is an Asian Echinacea. This plant is widely used in traditionnal remedies and folkloric medicines for thousands years and is reported to possess a wide spectrum of biological activities. A large number of diterpenoid ent-labdanes have been isolated from this plant, where the major compound is andrographolide, a diterpenoid lactone, that exhibits interesting anti-inflammatory activities on the NFB way. In order to understand and improve the anti-inflammatory activity of these compounds, we implemented a program aimed at their study. Qualitative analysis of crude extracts from dietary supplements allowed to obtain three major natural compounds, which were in a second time chemically modified. These products, as well as the crude extracts, where the composition was determined by a quantitative method, were used for the study of anti-inflammatory activity. Our aim was also to modify andrographolide on some positions not accessible by hemisynthesis. So total and enantioselective synthesis of andrographolide was investigated. Two ways were studied: biomimetic pathway, and modification of a bicyclic precursor that already possessed the ent-labdane configuration (Wieland-Miescher ketone). Methodology using Wieland-Miescher ketone was divided in three parts (enantioselective cyclisation, cycle A functionalisation, cycle B functionalisation). By this way, the bicyclic core was successfully functionnalised and analogues of andrographolide were prepared
Contribution of N-heterocyclic carbene-containing catalysts in the nucleoside chemistry
No full textCes dernières années, les analogues nucléosidiques ont eu un rôle majeur dans le traitement de maladies virales infectieuses tels le SIDA, les hépatites, l’herpès, la variole ou la grippe. Cependant, l’apparition de nouveaux virus ou de mutations virales ont renforcé la nécessité de développer des antiviraux plus efficaces et plus résistants. L’intensive recherche de dérivés nucléosidiques cliniquement actifs a permis l’émergence d’une multitude de nouvelles approches pour leurs synthèses. Parmi ce panel, les réactions catalysées par des métaux de transition tardifs font certainement partie des méthodes les plus importantes pour accéder à une large gamme de pharmacomodulations. Lors de ce projet de recherche, nous nous sommes intéressés à la conception, la synthèse et la découverte de nouveaux dérivés nucléosidiques en tant qu’antiviraux contre le virus de la variole. Pour ce faire, nous avons ciblé des 1,2,3-triazolo-carbanucléosides en série racémique ou énantiosélective ainsi que des nucléosides phosphonates acycliques. Dans un effort de développement et/ou d’amélioration de leurs méthodes de synthèse, nous avons également étudié la contribution de complexes au ruthénium et au cuivre contenant un carbène Nhétérocyclique (CNH) dans des réactions de métathèse croisée et de cycloaddition 1,3-dipolaire de Huisgen. Enfin, en vue d’obtenir des outils efficaces utilisables en synthèse nucléosidique, nous avons développés des nouveaux complexes au palladium portant un ligand CNH et testé leurs réactivités dans des réactions de Narylation de Buchwald-Hartwig et d’hydrogénation d’oléfines.In the last decades, nucleoside analogues have played a major role in the treatment of viral infectious diseases, such as AIDS, hepatitis, herpes, smallpox or influenza. Nevertheless, the apparition of new or mutated viruses highlights the need of more potent and resistant antiviral therapeutics. The intense search for clinically useful nucleoside derivatives has resulted in a wealth of new approaches for their synthesis. Among them, latetransition metal-catalyzed reactions are certainly the most important methods to access variety of appealing pharmacomodulations. In this research project, we were interested in the conception, the synthesis and the discovery of new nucleoside derivatives as antiviral agents against smallpox viruses. Hence, we have targeted racemic or enantiomerically pure 1,2,3-triazolo-carbanucleosides as well as acyclic nucleoside phosphonates. In our effort into the development or/and the improvement of their synthetic methodologies, we have also studied the contribution of ruthenium and copper complexes bearing N-heterocyclic carbene (NHC) ligands in cross-metathesis and Huisgen 1,3-dipolar cycloaddition reactions. Finally, in order to obtain efficient tools useful in nucleoside synthesis, we have developed new NHC-containing palladium complexes and examined their reactivity in Buchwald-Hartwig N-arylation and olefins hydrogenation reactions
Andrographis paniculata and its labdane diterpenes against oxidative stress and inflammation in skin aging.
No full textAvec l'âge et l'exposition à des facteurs environnementaux tels que les rayons solaires, la peau subit une usure naturelle. Elle se caractérise par l’apparition de rides, d’une perte d'élasticité, d’un relâchement et d’un aspect rugueux. Ce projet vise à explorer de nouveaux agents actifs anti-âges issus de la plante Andrographis paniculata (AP). AP est une plante médicinale utilisée en Asie pour traiter les infections respiratoires et diverses maladies inflammatoires. Cette plante est riche en diterpènes labdanes, dont son principal agent bioactif est l’andrographolide. Un extrait méthanolique des feuilles d’AP, l'andrographolide, la neoandrographolide, la 14-deoxyandrographolide et la 14-deoxy-11,12-didehydroandrographolide ont été utilisés dans une culture primaire de fibroblastes dermiques (HDFa) et une lignée cellulaire de kératinocytes (HaCaT). Pour l'étude du stress oxydant, ces cellules traitées dans des conditions pro-oxydantes ont révélé l'activité antioxydante de l'extrait méthanolique et de la 14-deoxyandrographolide. Dans des conditions pro-inflammatoires, l'expression du TNF-α a été diminuée par l'andrographolide et par l'extrait méthanolique dans les HDFa et par l’extrait méthanolique dans les HaCaT. L'andrographolide et l'extrait méthanolique ont également diminué la sécrétion d'IL-6 dans la HDFa dans des conditions inflammatoires. Enfin, la 14-désoxyandrographolide a réduit la production de procollagène de type I dans les HDFa. Nos données confirment leur potentiel régénérateur contre les dommages cutanés causés par le stress oxydant et l'inflammation. D'autres recherches sont nécessaires afin d’explorer ses voies.With age and exposure to environmental factors such as sunlight, the skin suffers natural wear and tear. It is characterized by development of wrinkles, loss of elasticity, laxity, and rough-textured appearance. The present project aims to explore new anti-aging active agents from Andrographis paniculata (AP) plant. AP is a medicinal plant used in Asia to treat respiratory infections and various inflammatory diseases. It is enriched in labdane diterpenes, including andrographolide, as its main bioactive agent. A methanolic extract from AP leaves, andrographolide, neoandrographolide, 14-deoxyandrographolide, and 14-deoxy-11,12-didehydroandrographolide were used in a primary culture of dermal fibroblasts (HDFa) and a keratinocyte cell line (HaCaT). For the oxidative stress study, HDFa and HaCaT treated under pro-oxidant conditions revealed the antioxidant activity of methanolic extract and 14-deoxyandrographolide. Under pro-inflammatory conditions, TNF-α expression was decreased in HDFa with andrographolide and methanolic extract, and in HaCaT with methanolic extract only. Andrographolide and methanolic extract also decreased IL-6 secretion in HDFa under inflammatory conditions. Finally, 14-deoxyandrographolide reduced the production of type I procollagen in HDFa. Our data confirm the AP potential skin damage regeneration induced by oxidative stress and inflammation. Further research is required to explore its pathways
Synthesis of Conjugated Dienes in Natural Compounds
No full textThis review describes the various synthetic methods commonly used to obtain molecules possessing conjugated dienes. We focus on methods involving cross-coupling reactions using various metals such as nickel, palladium, ruthenium, cobalt, cobalt/zinc, manganese, zirconium, or iron, mainly through examples that aimed to access natural molecules or their analogues. Among the natural molecules covered in this review, we discuss the total synthesis of a phytohormone, Acid Abscisic (ABA), carried out by our team involving the development of a conjugated diene chain
Catalyzed Mizoroki–Heck Reaction or C–H activation
No full textIn the last few decades, research on the elaboration by palladium-catalytic processes of C-C bonds or the activation of C–H bonds has increased considerably. Yet there is still room for much improvement in terms of selectivity, or enantioselectivity, via the development of new ligands or the study of the catalytic effect of other metals to carry out the same chemical transformations. In addition, the attention paid to environmentally friendly methods in terms of the quantities of catalysts, ligands, and solvents is currently indispensable. The Mizoroki-Heck reaction is one of these important catalytic methods which generates C-C bonds in organic synthesis and is also possible by C-H activation. This book, titled “Catalyzed Mizoroki-Heck Reaction or C-H activation” focuses on new advances in the formation of C-C bonds or new C-H activation methods. It contains original research papers and short reviews on the synthesis of biologically active compounds using these catalytic processes, the identification of new catalysts, of new conditions allowing selectivity or enantioselectivity, the activity and stability of catalyst under turnover conditions, and all improvements in catalytic processes
Comprehensive Overview of Antibacterial Drugs and Natural Antibacterial Compounds Found in Food Plants
No full textThe aim of this review is to list the various natural sources of antimicrobials that are readily available. Indeed, many plant sources are known to have antibiotic properties, although it is not always clear which molecule is responsible for this activity. Many food supplements also have this therapeutic indication. We propose here to take stock of the scientific knowledge attesting or not to these indications for some food sources. An overview of the various antibiotic drugs commercially available will be provided. A structural indication of the natural molecules present in various plants and reported to contribute to their antibiotic power will be given. The plants mentioned in this review, which does not claim to be exhaustive, are referenced for fighting Gram-positive and/or Gram-negative bacteria. It is difficult to attribute activity to just one of these natural molecules, as it is likely to result from synergy within the plant. Similarly, chitosan is mentioned for its fungistatic and bacteriostatic properties. In this case, this polymeric compound derived from the chitin of marine organisms is referenced for its antibiofilm activity. It seems that, in the face of growing antibiotic resistance, it makes sense to keep high-performance synthetic antibiotics on hand to treat the difficult pathologies that require them. On the other hand, for minor infections, the use of better-tolerated natural sources is certainly sufficient. To achieve this, we need to take stock of common plant sources, available as food products or dietary supplements, which are known to be active in this field
Microalgae, Cell Factories for Antimicrobial Peptides: A Promising Response to Antibiotic Resistance
No full textThe prevalence of infectious diseases is steadily increasing. If left untreated, they can lead to more serious health problems. Antibiotics currently available on the market are facing growing resistance, prompting the development of increasingly powerful antibacterial molecules. One alternative currently under investigation is the use of antibacterial peptides, whose mechanisms of action differ from those of conventional drugs. These peptides are produced naturally by all living organisms and can also be synthesized. However, as peptide chains become longer, synthesis and purification become increasingly complex and laborious. For decades, antimicrobial peptides have been synthesized on polymer supports using automated systems. Unfortunately, longer chains tend to fold more, preventing access of reagents within the cross-linked polymer network. Recombinant production of antimicrobial peptides has been achieved in various organisms called “cell factories,” allowing for more sustainable synthesis. Recently, microalgae have emerged as a promising and sustainable alternative for the production of antimicrobial peptides. They are inexpensive, easy to cultivate, and capable of producing biologically valuable molecules, offering a potential solution to antibiotic resistance. This work reviews the current state of these “cell factories” and examines the advantages and limitations of microalgae for the future of biopharmaceutical production
Catalyzed Mizoroki-Heck Reaction or C-H Activation
No full textIn the last few decade, research conducted on the development by catalytic processes of C-C bonds formation on the one hand and on the other hand on the activation of C-H bonds has grown considerably [...
Flavonoids and Furanocoumarins Involved in Drug Interactions
No full textDrug interactions can have significant consequences for public health, especially given the growing importance of readily available dietary supplements. The same applies to the consumption of fruit and fruit juices, which are often praised for their health benefits, but which can generate drug interactions. These are well known and documented in the case of grapefruit, which should not be taken with certain medications. Grapefruit contains flavonoids and furanocoumarins, which are responsible for various interactions with the cytochrome P450 enzyme system. However, for young children and the elderly, fruit juices are often used to facilitate treatment. This review examines commonly used fruit juices, particularly from citrus, apple, and red fruits, and discusses potential interactions, disadvantages, and advantages, as well as the chemical structures involved in interactions with cytochromes P-450, P-glycoprotein, and organic anion transporter polypeptide (OATP), responsible for sometimes dangerous changes in bioavailability or potential accumulation of drugs in the body
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