CNRS Molecular Pharmacochemistry Department

Grenoble, France

CNRS Molecular Pharmacochemistry Department

Grenoble, France
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Perez S.,CNRS Molecular Pharmacochemistry Department | De Sanctis D.,European Synchrotron Radiation Facility
Beilstein Journal of Organic Chemistry | Year: 2017

Synchrotron radiation is the most versatile way to explore biological materials in different states: monocrystalline, polycrystalline, solution, colloids and multiscale architectures. Steady improvements in instrumentation have made synchrotrons the most flexible intense X-ray source. The wide range of applications of synchrotron radiation is commensurate with the structural diversity and complexity of the molecules and macromolecules that form the collection of substrates investigated by glycoscience. The present review illustrates how synchrotron-based experiments have contributed to our understanding in the field of structural glycobiology. Structural characterization of protein-carbohydrate interactions of the families of most glycan-interacting proteins (including glycosyl transferases and hydrolases, lectins, antibodies and GAG-binding proteins) are presented. Examples concerned with glycolipids and colloids are also covered as well as some dealing with the structures and multiscale architectures of polysaccharides. Insights into the kinetics of catalytic events observed in the crystalline state are also presented as well as some aspects of structure determination of protein in solution. © 2017 Pérez and de Sanctis; licensee Beilstein-Institut.

Zongo F.,French Institute of Health and Medical Research | Zongo F.,University of Ouagadougou | Ribuot C.,University of Ouagadougou | Boumendjel A.,CNRS Molecular Pharmacochemistry Department | Guissou I.,University of Ouagadougou
Journal of Ethnopharmacology | Year: 2013

Ethnopharmacological relevance Waltheria indica L. (syn. Waltheria americana) is commonly used in traditional medicine in Africa, South America and Hawaii, mainly against pain, inflammation, conditions of inflammation, diarrhea, dysentery, conjunctivitis, wounds, abscess, epilepsy, convulsions, anemia, erectile dysfunctions, bladder ailments and asthma. Aim of the review to provide an up-to-date overview of the botany, phytochemistry, traditional uses, pharmacological activities and toxicity data of Waltheria indica. Additionally, studies providing an evidence for local and traditional uses of Waltheria indica are discussed. Further phytochemical and pharmacological potential of this species are suggested for future investigations. Materials and methods The information was collected from scientific journals, books, theses and reports via academic libraries and electronic search. These sources include Pubmed, Web of Science, Portal de Portales-Latindex, Science and Google scholar. These studies about the medical botanical, traditional uses, chemical, pharmacological and toxicological data on Waltheria indica were published in English, Portuguese, Spanish, German and French. Results Crude extracts and isolated compounds from Waltheria indica were investigated and showed analgesic, anti-inflammatory, antibacterial, antifungal, antimalarial, anti-anemic, anti-oxidant, sedative and anticonvulsant activities. The phytochemical investigations showed the presence of cyclopeptid alkaloids, flavonoids (e.g., (-)-epicatechin, quercetin, kaempferol, kaempferol-3-O-β-d-(6″-E-p- coumaryl)-glucopyranoside), tannins, sterols, terpenes, saponins, anthraquinones. Studies of acute toxicity in animal indicated that Waltheria indica can be toxic. Conclusion Waltheria indica possess therapeutic potential in the treatment of inflammation, malaria, infectious diseases (e.g., lungs infection due to Klebsiella pneumoniae, diarrhea due to Candida albicans or Escherichia coli) and prevention of oxidative stress. Further studies are necessary to explore pure compounds responsible for the pharmacological effects and the mechanisms of action. Further investigations are also needed to provide an evidence base for traditional uses of this species against pain, anemia, convulsions and epilepsy. In addition, there is a pressing need to investigate the other traditional uses such as dysentery, syphilis, erectile dysfunctions and asthma. © 2013 Elsevier Ireland Ltd. All rights reserved.

Wong Y.-S.,University Grenoble Alpes | Wong Y.-S.,CNRS Molecular Pharmacochemistry Department
Medecine/Sciences | Year: 2015

Structural diversity oriented synthesis aims to fulfill the unoccupied tridimensional "chemical space" gap left by traditional chemical libra-ries. Through the development of novel synthetic strategies relying on divergent reactions, chemist is now able to realize in only two or three steps such library that ensures the access of a large number of products having a good quality in term of structural diversity. A few examples are presented to illustrate how this can be done in the context of increasing molecular complexity and diversity devoted to the discovery and optimization of bioactive compounds. © 2015 médecine/sciences-Inserm.

Haudecoeur R.,CNRS Molecular Pharmacochemistry Department | Peuchmaur M.,CNRS Molecular Pharmacochemistry Department | Ahmed-Belkacem A.,French Institute of Health and Medical Research | Pawlotsky J.-M.,French Institute of Health and Medical Research | And 2 more authors.
Medicinal Research Reviews | Year: 2013

Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) possesses a single positive strand RNA genome encoding a polyprotein composed of approximatively 3000 amino acids. The polyprotein is cleaved at multiple sites by cellular and viral proteases to liberate structural and nonstructural (NS) proteins. NS5B, the RNA-dependent RNA polymerase (RdRp), which catalyzes the HCV RNA replication has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-acting antivirals). In the last 10 years, a growing number of non-nucleoside compounds have been reported as RdRp inhibitors and few are undergoing clinical trials. Over the past 5 years, several reviews were published all describing potentially active molecules. To the best of our knowledge, only one review covers the structure-activity relationships.1 In this review, we will discuss the reported non-nucleoside molecules acting as RdRp inhibitors according to their chemical class especially focusing on structure-activity relationship aspects among each class of compounds. Thereafter, we will attempt to address the global structural requirements needed for the design of specific inhibitors of RdRp. © 2012 Wiley Periodicals, Inc.

Szakacs G.,Hungarian Academy of Sciences | Hall M.D.,U.S. National Institutes of Health | Gottesman M.M.,U.S. National Institutes of Health | Boumendjel A.,CNRS Molecular Pharmacochemistry Department | And 6 more authors.
Chemical Reviews | Year: 2014

The development of multidrug resistance (MDR) in patients suffering cancer remains a significant clinical challenge, with drug efflux by ABC (ATP-binding cassette) transporters contributing significantly. Theoretically, one could restore the efficacy of first-line drugs by circumventing these resistance mechanisms. However, cancer is a heterogeneous disease that can exhibit different characteristics from patient to patient or even within a single patient. Spatial and temporal heterogeneity is a result of continuous adaptation to selective pressures through sequential genetic changes that ultimately convert a normal cell into intractable cancer. Thus, cancer cells are moving targets, as individual cells in a tumor mass constantly adapt to local environmental challenges. Biological membranes represent a significant permeation barrier and thus play a critical role in the protection of pharmacokinetic compartments. Conversely, the activity of a drug ultimately depends on the ability of the compound to reach its target, which might reside in a well-protected pharmacological sanctuary.

Wong Y.-S.,CNRS Molecular Pharmacochemistry Department
Methods in Molecular Biology | Year: 2012

Recent advances and concepts for exploring chemical space are highlighted in this chapter and show how the synthetic chemical world meets the demand of making large and relevant collection of new molecules for analyzing the biological world more closely. © 2012 Springer Science+Business Media, LLC.

Haudecoeur R.,CNRS Molecular Pharmacochemistry Department | Boumendjel A.,CNRS Molecular Pharmacochemistry Department
Current Medicinal Chemistry | Year: 2012

The first review regarding the potential of aurones as promising drug candidates was reported in 2003. Since, considerable efforts have been made to explore the pharmacological and therapeutical activities of aurones. In this regard, many biological areas were concerned, including major pathological, such as cancer and neurodegenerative disorders. The aim of the present report is to highlight the progress made during the last ten years on the medicinal chemistry of aurones. A special focus will be made on the structure-activity relationship aspects among aurones and especially in case where aurones were found highly active than the corresponding flavones and chalcones. © 2012 Bentham Science Publishers.

Nicolle E.,CNRS Molecular Pharmacochemistry Department | Souard F.,CNRS Molecular Pharmacochemistry Department | Faure P.,French Institute of Health and Medical Research | Boumendjel A.,CNRS Molecular Pharmacochemistry Department
Current Medicinal Chemistry | Year: 2011

There is evidence that hyperglycemia results in the generation of reactive oxygen species, leading to oxidative stress in various tissues, including vascular system. An important link between oxidative stress, inflammatory response and insulin activity is now well established. The ability of antioxidants to protect against the deleterious effects of hyperglycemia and also to improve glucose metabolism and intake must be considered as leads of choice in diabetes treatment. In addition to their antioxidative activity, many flavonoids were demonstrated to act on biological targets involved in type 2 diabetes mellitus such as: glycosidase, glucose cotransporter or aldose reductase. In this context, flavonoids behaving as antioxidants were studied as potential drugs by acting as biological targets involved in diabetes development. In this review, we propose to shed light on antioxidants flavonoids investigated as antidiabetics. A special focus was made to address the structure-activity relationship related to the effect of these naturally occurring molecules on different targets involved in diabetes development. © 2011 Bentham Science Publishers Ltd.

Demeunynck M.,CNRS Molecular Pharmacochemistry Department | Baussanne I.,CNRS Molecular Pharmacochemistry Department
Current Medicinal Chemistry | Year: 2013

the present review focuses on the synthesis and biological evaluation of polycyclic 4(3H)-quinazolinones containing fused aromatic or heteroaromatic rings. The first part of the review is related to compounds with ring fused to the pyrimidine part of the quinazoline core. Most of the quinazolinone alkaloids belong to this class of molecules. The second part presents molecules bearing extra ring(s) fused to the benzo moiety of the quinazolinone skeleton. Their structural diversity opens new fields in the search of active molecules. © 2013 Bentham Science Publishers.

Genoux E.,CNRS Molecular Pharmacochemistry Department | Nicolle E.,CNRS Molecular Pharmacochemistry Department | Boumendjel A.,CNRS Molecular Pharmacochemistry Department
Current Organic Chemistry | Year: 2011

The cancer preventing effect of flavonoids is largely documented in literature. In addition to their nutritional value as cancer preventing agents, they have been studied as drug candidates in cancer treatment. Many mechanisms of action have been identified, including carcinogen inactivation, antiproliferation, cell cycle arrest, induction of apoptosis and differentiation, inhibition of angiogenesis, antioxidative activity and reversal of multidrug resistance. The diversity in the biological targets of flavonoids has led during the last twenty years to an extensive research toward medicinal chemistry of flavonoids with the aim to obtain anticancer drugs. Some anticancer agents derived from flavonoids are emerging as major anticancer drugs or chemosensitizers. This review will shed light on recent molecules obtained from efforts made on medicinal chemistry of flavonoids. A special focus will be made on flavonoid derivatives being studied in clinical trials. © 2011 Bentham Science Publishers Ltd.

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