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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.

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.

Perez S.,CNRS Molecular Pharmacochemistry Department | Tvaroska I.,Slovak Academy of Sciences | Tvaroska I.,Constantine the Philosopher University
Advances in Carbohydrate Chemistry and Biochemistry | Year: 2014

The article reviews the significant contributions to, and the present status of, applications of computational methods for the characterization and prediction of protein-carbohydrate interactions. After a presentation of the specific features of carbohydrate modeling, along with a brief description of the experimental data and general features of carbohydrate-protein interactions, the survey provides a thorough coverage of the available computational methods and tools. At the quantum-mechanical level, the use of both molecular orbitals and density-functional theory is critically assessed. These are followed by a presentation and critical evaluation of the applications of semiempirical and empirical methods: QM/MM, molecular dynamics, free-energy calculations, metadynamics, molecular robotics, and others. The usefulness of molecular docking in structural glycobiology is evaluated by considering recent docking- validation studies on a range of protein targets. The range of applications of these theoretical methods provides insights into the structural, energetic, and mechanistic facets that occur in the course of the recognition processes. Selected examples are provided to exemplify the usefulness and the present limitations of these computational methods in their ability to assist in elucidation of the structural basis underlying the diverse function and biological roles of carbohydrates in their dialogue with proteins. These test cases cover the field of both carbohydrate biosynthesis and glycosyltransferases, as well as glycoside hydrolases. The phenomenon of (macro)molecular recognition is illustrated for the interactions of carbohydrates with such proteins as lectins, monoclonal antibodies, GAG-binding proteins, porins, and viruses. © 2014 Elsevier 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.

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.

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