Author
Isabelle Parrot
Bio: Isabelle Parrot is an academic researcher from University of Montpellier. The author has contributed to research in topics: Protein–protein interaction & Peptide sequence. The author has an hindex of 8, co-authored 19 publications receiving 367 citations.
Papers
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TL;DR: This review aims to be a comprehensive and general summary of the different isoxazolidine syntheses, their use as starting building blocks for the preparation of natural compounds, and their main biological activities.
Abstract: The isoxazolidine ring represents one of the privileged structures in medicinal chemistry, and there have been an increasing number of studies on isoxazolidine and isoxazolidine-containing compounds. Optimization of the 1,3-dipolar cycloaddition (1,3-DC), original methods including electrophilic or palladium-mediated cyclization of unsaturated hydroxylamine, has been developed to obtain isoxazolidines. Novel reactions involving the isoxazolidine ring have been highlighted to accomplish total synthesis or to obtain bioactive compounds, one of the most significant examples being probably the thermic ring contraction applied to the total synthesis of (±)-Gelsemoxonine. The unique isoxazolidine scaffold also exhibits an impressive potential as a mimic of nucleosides, carbohydrates, PNA, amino acids, and steroid analogs. This review aims to be a comprehensive and general summary of the different isoxazolidine syntheses, their use as starting building blocks for the preparation of natural compounds, and their m...
176 citations
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TL;DR: The results identify the first set of drug-like compounds that functionally target the HIV-1 Nef SH3 binding surface and provide the basis for a powerful discovery process that should help to speed up 2P2I strategies and open avenues for new class of antiviral molecules.
Abstract: Protein–protein recognition is the cornerstone of multiple cellular and pathological functions. Therefore, protein–protein interaction inhibition (2P2I) is endowed with great therapeutic potential despite the initial belief that 2P2I was refractory to small-molecule intervention. Improved knowledge of complex molecular binding surfaces has recently stimulated renewed interest for 2P2I, especially after identification of “hot spots” and first inhibitory compounds. However, the combination of target complexity and lack of starting compound has thwarted experimental results and created intellectual barriers. Here we combined virtual and experimental screening when no previously known inhibitors can be used as starting point in a structure-based research program that targets an SH3 binding surface of the HIV type I Nef protein. High-throughput docking and application of a pharmacophoric filter on one hand and search for analogy on the other hand identified drug-like compounds that were further confirmed to bind Nef in the micromolar range (isothermal titration calorimetry), to target the Nef SH3 binding surface (NMR experiments), and to efficiently compete for Nef–SH3 interactions (cell-based assay, GST pull-down). Initial identification of these compounds by virtual screening was validated by screening of the very same library of compounds in the cell-based assay, demonstrating that a significant enrichment factor was attained by the in silico screening. To our knowledge, our results identify the first set of drug-like compounds that functionally target the HIV-1 Nef SH3 binding surface and provide the basis for a powerful discovery process that should help to speed up 2P2I strategies and open avenues for new class of antiviral molecules.
128 citations
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TL;DR: This powerful ring contraction allows for example the one-step synthesis of various tetramic acids, access to 2-disubstituted statins, or the synthesis of relevant lactam-constrained dipeptide mimetics using a TRAL-RCM sequence.
Abstract: An efficient and original stereocontrolled transannular rearrangement starting from activated 2,5-diketopiperazines has been developed, an opportunity for the medicinal chemistry field, which requests access to novel biological scaffolds. This powerful ring contraction, which can be related to a stereoselective aza-version of the Chan rearrangement, allows for example the one-step synthesis of various tetramic acids, access to 2-disubstituted statins, or the synthesis of relevant lactam-constrained dipeptide mimetics using a TRAL–RCM sequence.
31 citations
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TL;DR: This review constitutes the first critical compilation on oyster shell applications, with the aim to provide essential elements to better comprehend the recycling of waste oyster shells.
Abstract: Oyster farming represents one of the most developed aquaculture activities, producing delicacies unfortunately related to a direct accumulation of waste shells. Facing what is becoming an environmental issue, chemists are currently developing solutions to add value to this wild source of raw material in line with the principles of sustainable chemistry. An argumentative overview of this question is proposed here with a focus on recent data. Starting with a presentation of the environmental impact of oyster farming, existing and promising applications are then classified according to the type of raw materials derived from the oyster shell, namely the natural oyster shell (NOS), the calcined natural oyster shell (CNOS), and biomolecules of the organic matrix extracted from the oyster shell. Their relevance is discussed in regard to their scalability, originality, and sustainability. This review constitutes the first critical compilation on oyster shell applications, with the aim to provide essential elements to better comprehend the recycling of waste oyster shells.
24 citations
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TL;DR: Ring contraction of 2,5-diketopiperazines by TRAL-alkylation led to the stereoselective synthesis of original pyrrolidine-2,4-diones, a novel series of promising molecules with moderate anti-proliferative activity on breast cancer cells.
19 citations
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TL;DR: This review aims to highlight the recent evidence of chalcone as a privileged scaffold in medicinal chemistry and is expected to be a comprehensive, authoritative, and critical review of the chal cone template to the chemistry community.
Abstract: Privileged structures have been widely used as an effective template in medicinal chemistry for drug discovery. Chalcone is a common simple scaffold found in many naturally occurring compounds. Many chalcone derivatives have also been prepared due to their convenient synthesis. These natural products and synthetic compounds have shown numerous interesting biological activities with clinical potentials against various diseases. This review aims to highlight the recent evidence of chalcone as a privileged scaffold in medicinal chemistry. Multiple aspects of chalcone will be summarized herein, including the isolation of novel chalcone derivatives, the development of new synthetic methodologies, the evaluation of their biological properties, and the exploration of the mechanisms of action as well as target identification. This review is expected to be a comprehensive, authoritative, and critical review of the chalcone template to the chemistry community.
800 citations
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645 citations
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TL;DR: Examples of the synergistic use of SAXS with high resolution methods like X‐ray crystallography and nuclear magnetic resonance (NMR), as well as other experimental andin silico techniques to characterize completely, or partially unstructured proteins, are presented.
475 citations
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TL;DR: An overview of the current computational drug design and their application in integrated rational drug development to aid in the progress of drug discovery research is given.
Abstract: Drug discovery utilizes chemical biology and computational drug design approaches for the efficient identification and optimization of lead compounds. Chemical biology is mostly involved in the elucidation of the biological function of a target and the mechanism of action of a chemical modulator. On the other hand, computer-aided drug design makes use of the structural knowledge of either the target (structure-based) or known ligands with bioactivity (ligand-based) to facilitate the determination of promising candidate drugs. Various virtual screening techniques are now being used by both pharmaceutical companies and academic research groups to reduce the cost and time required for the discovery of a potent drug. Despite the rapid advances in these methods, continuous improvements are critical for future drug discovery tools. Advantages presented by structure-based and ligand-based drug design suggest that their complementary use, as well as their integration with experimental routines, has a powerful impact on rational drug design. In this article, we give an overview of the current computational drug design and their application in integrated rational drug development to aid in the progress of drug discovery research.
400 citations