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21 results on '"Andrii Karpus"'

1. Effects of Cationic Dendrimers and Their Complexes with microRNAs on Immunocompetent Cells

Author

Nadezhda Knauer, Ekaterina Pashkina, Alina Aktanova, Olga Boeva, Valeria Arkhipova, Margarita Barkovskaya, Mariya Meschaninova, Andrii Karpus, Jean-Pierre Majoral, Vladimir Kozlov, and Evgeny Apartsin

Subjects
dendrimers, microRNA, immunotherapy, nanomedicine, PBMCs, cytokines, Pharmacy and materia medica, RS1-441
Abstract

Short regulatory oligonucleotides are considered prospective tools for immunotherapy. However, they require an adequate carrier to deliver potential therapeutics into immune cells. Herein, we explore the potential of polycationic dendrimers as carriers for microRNAs in peripheral blood mononuclear cells of healthy donors. As an oligonucleotide cargo, we use a synthetic mimic and an inhibitor of miR-155, an important factor in the development and functioning of immunocompetent cells. Dendrimers bind microRNAs into low-cytotoxic polyelectrolyte complexes that are efficiently uptaken by immunocompetent cells. We have shown these complexes to affect the number of T-regulatory cells, CD14+ and CD19+ cell subpopulations in non-activated mononuclear cells. The treatment affected the expression of HLA-DR on T-cells and PD-1 expression on T- and B-lymphocytes. It also affected the production of IL-4 and IL-10, but not the perforin and granzyme B production. Our findings suggest the potential of dendrimer-mediated microRNA-155 treatment for immunotherapy, though the activity of microRNA-dendrimer constructions on distinct immune cell subsets can be further improved.

Published
2022
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2. Functionalized Dendrimer Platforms as a New Forefront Arsenal Targeting SARS-CoV-2: An Opportunity

Author

Serge Mignani, Xiangyang Shi, Andrii Karpus, Giovanni Lentini, and Jean-Pierre Majoral

Subjects
COVID-19 pandemic, SARS-CoV-2, nanotechnology, dendrimers, repurposing strategy, Pharmacy and materia medica, RS1-441
Abstract

The novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a pandemic. There are currently several marketed vaccines and many in clinical trials targeting SARS-CoV-2. Another strategy is to repurpose approved drugs to decrease the burden of the COVID-19 (official name for the coronavirus disease) pandemic. as the FDA (U.S. Food and Drug Administration) approved antiviral drugs and anti-inflammatory drugs to arrest the cytokine storm, inducing the production of pro-inflammatory cytokines. Another view to solve these unprecedented challenges is to analyze the diverse nanotechnological approaches which are able to improve the COVID-19 pandemic. In this original minireview, as promising candidates we analyze the opportunity to develop biocompatible dendrimers as drugs themselves or as nanocarriers against COVID-19 disease. From the standpoint of COVID-19, we suggest developing dendrimers as shields against COVID-19 infection based on their capacity to be incorporated in several environments outside the patients and as important means to stop transmission of SARS-CoV-2.

Published
2021
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3. Amphiphilic Phosphorus Dendrons Associated with Anti-inflammatory siRNA Reduce Symptoms in Murine Collagen-Induced Arthritis

Author

Zhibo Yu, Nicolas Tsapis, François Fay, Liang Chen, Andrii Karpus, Xiangyang Shi, Catherine Cailleau, Samuel García Pérez, Nicolas Huang, Juliette Vergnaud, Serge Mignani, Jean-Pierre Majoral, and Elias Fattal

Subjects
Biomaterials, Polymers and Plastics, Materials Chemistry, Bioengineering
Abstract

Small interfering RNA (siRNA) holds promise for treating rheumatoid arthritis by inhibiting major cytokines such as tumor necrosis factor-α (TNF-α). We developed original cationic amphiphilic phosphorus dendrons to produce dendriplexes associated with TNF-α siRNA. The dendrons were made of 10 pyrrolidinium end groups and a C17 aliphatic chain. The dendriplexes demonstrated the ability to protect siRNA from nuclease degradation and to promote macrophage uptake. Moreover, they led to potent inhibition of TNF-α expression in the lipopolysaccharide-activated mouse macrophage cell line RAW264.7 in vitro model. A significant anti-inflammatory effect in the murine collagen-induced arthritis model was observed through arthritis scoring and histological observations. These results open up essential perspectives in using this original amphiphilic dendron to reduce the disease burden and improve outcomes in chronic inflammatory diseases.

Published
2023
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4. Clinical diagonal translation of nanoparticles: Case studies in dendrimer nanomedicine

Author

Gang Zheng, Serge Mignani, Jean-Pierre Majoral, Andrii Karpus, Keegan Guidolin, and Xiangyang Shi

Subjects
Dendrimers, Drug Carriers, Computer science, Drug Compounding, Pharmaceutical Science, Nanoparticle, Nanotechnology, Polymeric nanoparticles, Nanomedicine, Dendrimer, Nanoparticles, Nanocarriers, Drug carrier
Abstract

Among the numerous nanomedicine formulations, dendrimers have emerged as original, efficient, carefully assembled, hyperbranched, polymeric nanoparticles based on synthetic monomers. Dendrimers are used either as nanocarriers of drugs or as drugs themselves. When used as drug carriers, dendrimers are considered 'best-in-class agents', modifying and enhancing the pharmacokinetic and pharmacodynamic properties of the active entities encapsulated or conjugated with the dendrimers. When used as drugs themselves, dendrimers represent a novel category of "first-in-class" drugs. The purpose of this original review is to analyse the different strategies involved in the development, application, and impact of dendrimers as drugs. We examine a selection of nanoparticles that use multifunctional elements and demonstrate clinical multifunctionality, and we extend these principles to applications in dendrimer nanomedicine design. Finally, for practical consideration, the concepts of vertical and diagonal translation are introduced as potential strategies to facilitate dendrimer development.

Published
2021
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5. Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death

Author

Inmaculada Posadas, Laura Romero-Castillo, Rosa-Anna Ronca, Andrii Karpus, Serge Mignani, Jean-Pierre Majoral, Mariángeles Muñoz-Fernández, Valentín Ceña, Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est (UPE), Centro de Química da Madeira, Universidade da Madeira (UMA), Hospital General Universitario 'Gregorio Marañón' [Madrid], European Union NextGenerationEU (PRTR-C17.I1), Spanish Ministerio de Ciencia e Innnovación (project PID2020-120134RBI00 from MINECO/AEI/FEDER/UE), Instituto de Salud Carlos III (ISCIII, projects RETIC PT17/0015/0042, PI19/01638), Junta de Comunidades de Castilla-La Mancha (project SBPLY/19/180501/000067), ERANET Euronanomed Program (project NANO4GLIO), Action Nano2Clinic (CA17140) / COST, CNRS, FCT-Fundação para a Ciência e a Tecnologia (Base Fund UIDB/00674/2020 and Programmatic Fund UIDP/00674/2020, Portuguese Government Funds), and ARDITI-Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação through the project M1420-01-0145-FEDER-000005-CQM+ (Madeira 14-20 Program)

Subjects
Cortical neurons, Dendrimers, N-Methylaspartate, Glutamic Acid, Phosphorous dendrimers, Receptors, N-Methyl-D-Aspartate, Catalysis, Inorganic Chemistry, Brain organoids, Mice, Animals, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Excitotoxicity, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Cells, Cultured, Neurons, Organic Chemistry, Brain, General Medicine, Neuroprotection, Mitochondria, Computer Science Applications, Rats, Organoids, Neuroprotective Agents, phosphorous dendrimers, excitotoxicity, cortical neurons, brain organoids, neuroprotection, mitochondria, Receptors, Glutamate
Abstract

International audience; Nanoparticles are playing an increasing role in biomedical applications. Excitotoxicity plays a significant role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. Glutamate ionotropic receptors, mainly those activated by N-methyl-D-aspartate (NMDA), play a key role in excitotoxic death by increasing intraneuronal calcium levels; triggering mitochondrial potential collapse; increasing free radicals; activating caspases 3, 9, and 12; and inducing endoplasmic reticulum stress. Neutral phosphorous dendrimers, acting intracellularly, have neuroprotective actions by interfering with NMDA-mediated excitotoxic mechanisms in rat cortical neurons. In addition, phosphorous dendrimers can access neurons inside human brain organoids, complex tridimensional structures that replicate a significant number of properties of the human brain, to interfere with NMDA-induced mechanisms of neuronal death. Phosphorous dendrimers are one of the few nanoparticles able to gain access to the inside of neurons, both in primary cultures and in brain organoids, and to exert pharmacological actions by themselves.

Published
2022
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7. Functionalized Dendrimer Platforms as a New Forefront Arsenal Targeting SARS-CoV-2: An Opportunity

Author

Giovanni Lentini, Jean-Pierre Majoral, Xiangyang Shi, Serge Mignani, Andrii Karpus, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centro de Química da Madeira, Universidade da Madeira (UMA), College of Chemistry, Chemical Engineering and Biotechnology, Donghua University (CCEB), Donghua University [Shanghai], Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), PRC NSFC-CNRS 2019, CNRS, EuroNanoMed III Project (European Union’s Horizon 2020 research and innovation, grant agreement no 723770), FCT-Fundação para a Ciência e a Tecnologia (Base Fund UIDB/00674/2020 and Programmatic Fund UIDP/00674/2020, PortugueseGovernment Funds), and ARDITI-Agência Regional para o Desenvolvimento da Investigação Tecnologia e Inovação through the project M1420-01-0145-FEDER-000005-CQM+ (Madeira 14–20 Program)

Subjects
Coronavirus disease 2019 (COVID-19), nanotechnology, business.industry, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pharmaceutical Science, COVID-19 pandemic, Review, medicine.disease_cause, Biocompatible material, medicine.disease, Human coronavirus, Virology, dendrimers, RS1-441, Pharmacy and materia medica, repurposing strategy, Pandemic, medicine, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Nanocarriers, business, Cytokine storm, Coronavirus
Abstract

International audience; The novel human coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has caused a pandemic. There are currently several marketed vaccines and many in clinical trials targeting SARS-CoV-2. Another strategy is to repurpose approved drugs to decrease the burden of the COVID-19 (official name for the coronavirus disease) pandemic. as the FDA (U.S. Food and Drug Administration) approved antiviral drugs and anti-inflammatory drugs to arrest the cytokine storm, inducing the production of pro-inflammatory cytokines. Another view to solve these unprecedented challenges is to analyze the diverse nanotechnological approaches which are able to improve the COVID-19 pandemic. In this original minireview, as promising candidates we analyze the opportunity to develop biocompatible dendrimers as drugs themselves or as nanocarriers against COVID-19 disease. From the standpoint of COVID-19, we suggest developing dendrimers as shields against COVID-19 infection based on their capacity to be incorporated in several environments outside the patients and as important means to stop transmission of SARS-CoV-2.

Published
2021
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8. First-in-class and best-in-class dendrimer nanoplatforms from concept to clinic: Lessons learned moving forward

Author

Helena Tomás, Jean-Pierre Majoral, Serge Mignani, Xangyang Shi, Andrii Karpus, João Rodrigues, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centro de Química da Madeira, Universidade da Madeira (UMA), College of Chemistry, Chemical Engineering and Biotechnology, Donghua University (CCEB), Donghua University [Shanghai], Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), PRC NSFC-CNRS 2019 (21911530230, 199675), FCT-Fundaçao para a Ciencia e a Tecnologia (Base Fund UIDB/00674/2020 and Programmatic Fund UIDP/00674/2020, Portuguese Government Funds), ARDITI-Agencia Regional para o Desenvolvimento da Investigaçao Tecnologia e Inovaçao (project M1420-01-0145-FEDER-000005-CQMþ (Madeira 14e20 Program)), CNRS (France), EuroNanoMed III European Innovative research and technological development project in Nanomedicine JTC 2019: Project NANOmedicinefor Glioblastoma therapy NANO4 GLIO, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Dendrimers, Biocompatible Materials, 01 natural sciences, 03 medical and health sciences, Human health, Dendrimer, Drug Discovery, Humans, [CHIM.COOR]Chemical Sciences/Coordination chemistry, 030304 developmental biology, Pharmacology, Drug Carriers, 0303 health sciences, Class (computer programming), 010405 organic chemistry, Management science, Chemistry, Organic Chemistry, General Medicine, 0104 chemical sciences, 3. Good health, Drug Liberation, Nanomedicine, Pharmaceutical Preparations, Nanocarriers, Half-Life
Abstract

International audience; Research to develop active dendrimers by themselves or as nanocarriers represents a promising approach to discover new biologically active entities that can be used to tackle unmet medical needs including difficult diseases. These developments are possible due to the exceptional physicochemical properties of dendrimers, including their biocompatibility, as well as their therapeutic activity as nanocarriers and drugs themselves. Despite a large number of academic studies, very few dendrimers have crossed the ‘valley of death’ between. Only a few number of pharmaceutical companies have succeeded in this way. In fact, only Starpharma (Australia) and Orpheris, Inc. (USA), an Ashvattha Therapeutics subsidiary, can fill all the clinic requirements to have in the market dendrimers based drugs/nancocarriers. After evaluating the main physicochemical properties related to the respective biological activity of dendrimers classified as first-in-class or best-in-class in nanomedicine, this original review analyzes the advantages and disavantages of these two strategies as well the concerns to step in clinical phases. Various solutions are proposed to advance the use of dendrimers in human health.

Published
2021
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9. Chiral phosphorus-containing calixarenes

Author

Andrii Karpus, Oleksandr Yesypenko, Sergii Cherenok, Vyacheslav Boiko, Olga Kalchenko, Zoia Voitenko, Oleksandr Trybrat, Rinaldo Poli, Jean-Claude Daran, Eric Manoury, Vitaly Kalchenko, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institute of Organic Chemistry, National Academy of Sciences of Ukraine, National Academy of Sciences of Ukraine (NASU), Taras Shevchenko National University of Kyiv, Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Phosphines, 010405 organic chemistry, Organic Chemistry, Stereoselective synthesis, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, 0104 chemical sciences, 3. Good health, Inorganic Chemistry, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Calixarenes, Phosphonates, Chirality
Abstract

International audience; Phosphorus-containing inherently chiral calix[4]arenes as well as calix[4]arenes substituted with phosphinoferrocene chiral groups at the lower rim are described. Stereoselective synthesis, structure, and catalytic properties of the chiral calixarenes are discussed.

Published
2019
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10. Safe Polycationic Dendrimers as Potent Oral In Vivo Inhibitors of Mycobacterium tuberculosis : A New Therapy to Take Down Tuberculosis

Author

Andrii Karpus, Régis Laurent, Shriya Singh, Vishwa Deepak Tripathi, Jean-Pierre Majoral, Kishore K. Srivastava, Dheerj Soam, Anke Steinmetz, Ramakrishna Gandikota, Serge Mignani, Anne-Marie Caminade, Rama P. Tripathi, Swetarka Das, Arunava Dasgupta, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centro de Química da Madeira, Universidade da Madeira (UMA), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CSIR-Central Drug Research Institute (CSIR-CDRI), Council of Scientific and Industrial Research [India] (CSIR), Sanofi R & D, Integrated Drug Discovery, In Vitro Biology & Pharmacology, CSIR-CDRI, FCT-Fundacao para a Ciencia e a Tecnologia (project PEst-OE/QUI/UI0674/2013, CQM, Portuguese Government funds), ARDITI (project M1420-01-0145-FEDER-000005-Centro de Quimica da Madeira-CQM+ (Madeira 14-20)), Centre National de la Recherche Scientifique (CNRS, France), Indo-French CEFIPRA (project CEFIPRA-5303-2), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Drug, Tuberculosis, Polymers and Plastics, media_common.quotation_subject, Bioengineering, 02 engineering and technology, Pharmacology, 010402 general chemistry, 01 natural sciences, Biomaterials, Mycobacterium tuberculosis, In vivo, Oral administration, Materials Chemistry, medicine, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Ethambutol, media_common, Dendrons, biology, Bacteria, Chemistry, Phosphorus, 021001 nanoscience & nanotechnology, medicine.disease, biology.organism_classification, 0104 chemical sciences, 3. Good health, Streptomycin, Infectious diseases, Pharmaceuticals, 0210 nano-technology, Rifampicin, medicine.drug
Abstract

International audience; The long-term treatment of tuberculosis (TB) sometimes leads to nonadherence to treatment, resulting in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. Inadequate bioavailability of the drug is the main factor for therapeutic failure, which leads to the development of drug-resistant cases. Therefore, there is an urgent need to design and develop novel antimycobacterial agents minimizing the period of treatment and reducing the propagation of resistance at the same time. Here, we report the development of original and noncytotoxic polycationic phosphorus dendrimers essentially of generations 0 and 1, but also of generations 2–4, with pyrrolidinium, piperidinium, and related cyclic amino groups on the surface, as new antitubercular agents active per se, meaning with intrinsic activity. The strategy is based on the phenotypic screening of a newly designed phosphorus dendrimer library (generations 0–4) against three bacterial strains: attenuated Mycobacterium tuberculosis H37Ra, virulent M. tuberculosis H37Rv, and Mangora bovis BCG. The most potent polycationic phosphorus dendrimers 1G0,HCl and 2G0,HCl are active against all three strains with minimum inhibitory concentrations (MICs) between 3.12 and 25.0 μg/mL. Both are irregularly shaped nanoparticles with highly mobile branches presenting a radius of gyration of 7 Å, a diameter of maximal 25 Å, and a solvent-accessible surface area of dominantly positive potential energy with very localized negative patches arising from the central N3P3 core, which steadily interacts with water molecules. The most interesting is 2G0,HCl, showing relevant efficacy against single-drug-resistant (SDR) M. tuberculosis H37Rv, resistant to rifampicin, isoniaid, ethambutol, or streptomycin. Importantly, 2G0,HCl displayed significant in vivo efficacy based on bacterial counts in lungs of infected Balb/C mice at a dose of 50 mg/kg oral administration once a day for 2 weeks and superior efficacy in comparison to ethambutol and rifampicin. This series of polycationic phosphorus dendrimers represents first-in-class drugs to treat TB infection, could fulfill the clinical candidate pipe of this high burden of infectious disease, and play a part in addressing the continuous demand for new drugs.

Published
2021
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11. Safe Polycationic Dendrimers as Potent Oral In Vivo Inhibitors of

Author

Serge, Mignani, Vishwa Deepak, Tripathi, Dheerj, Soam, Rama Pati, Tripathi, Swetarka, Das, Shriya, Singh, Ramakrishna, Gandikota, Regis, Laurent, Andrii, Karpus, Anne-Marie, Caminade, Anke, Steinmetz, Arunava, Dasgupta, Kishore Kumar, Srivastava, and Jean-Pierre, Majoral

Subjects
Dendrimers, Mice, Antitubercular Agents, Animals, Tuberculosis, Microbial Sensitivity Tests, Mycobacterium tuberculosis
Abstract

The long-term treatment of tuberculosis (TB) sometimes leads to nonadherence to treatment, resulting in multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. Inadequate bioavailability of the drug is the main factor for therapeutic failure, which leads to the development of drug-resistant cases. Therefore, there is an urgent need to design and develop novel antimycobacterial agents minimizing the period of treatment and reducing the propagation of resistance at the same time. Here, we report the development of original and noncytotoxic polycationic phosphorus dendrimers essentially of generations 0 and 1, but also of generations 2-4, with pyrrolidinium, piperidinium, and related cyclic amino groups on the surface, as new antitubercular agents active

Published
2021

12. Well-Defined P III -Terminated Polymers from Phosphorylated Carbodithioate RAFT Agents

Author

Andrii Karpus, Eric Manoury, Rinaldo Poli, Simon Harrisson, Mathias Destarac, Stéphane Mazières, Laboratoire de chimie de coordination (LCC), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie des Polymères Organiques (LCPO), Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Team 1 LCPO : Polymerization Catalyses & Engineering, Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), P3R - Polymères de Précision par Procédés Radicalaires (P3R), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Centre National de la Recherche Scientifique (CNRS), ANR-16-CE29-0014,RAFTSWITCH,Agents de Transfert RAFT Modulables pour la Polymérisation Radicalaire Contrôlée.(2016), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC), and Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Polytechnique de Bordeaux-Ecole Nationale Supérieure de Chimie, de Biologie et de Physique (ENSCBP)-Université de Bordeaux (UB)-Institut de Chimie du CNRS (INC)

Subjects
Polymers and Plastics, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Inorganic Chemistry, chemistry.chemical_compound, Polymer chemistry, Materials Chemistry, Vinyl acetate, Reversible addition−fragmentation chain-transfer polymerization, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Nuclear magnetic resonance spectroscopy, chemistry.chemical_classification, Acrylate, RAFT polymerization, Chemistry, Organic Chemistry, Leaving group, Chain transfer, Polymer, 021001 nanoscience & nanotechnology, Phosphorylated carbodithioates, 3. Good health, 0104 chemical sciences, Monomer, [CHIM.POLY]Chemical Sciences/Polymers, Polymerization, 0210 nano-technology
Abstract

International audience; Five S-alkyl di-tert-butylphosphorylated carbodithioates, Z–C(S)SR, were studied as chain transfer agents (CTAs) in the RAFT polymerization of vinyl monomers. These phosphorus-containing CTAs involve new PIII and PV moieties in the Z group (phosphine-borane or free phosphine). Two of them, with an S-bonded 1-methoxycarbonylethyl group as leaving group, have not previously been described. The CTAs with a PV Z group provide good control over the polymerization of styrene (St) and n-butyl acrylate (nBA). Molar masses are close to theoretical values, and dispersities are consistently low during polymerization. The monitoring of polymerization by 31P NMR spectroscopy supports the controlled character and the integrity of the polymer chain ends. Conversely, they inhibit the polymerization of the less-activated monomer vinyl acetate (VAc). The reactivity of the CTAs with a PIII Z group mainly depends on the reaction medium, and their performance for St, nBA, and VAc was surprising and unexpected. Theoretical calculations were carried out to rationalize their behavior. Finally, an innovative strategy was developed to obtain well-controlled polymers with free phosphine ω-chain ends.

Published
2021
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13. Manganese phosphinocarbodithioate for RAFT polymerisation with sunlight-induced chain end post-treatment

Author

Stéphane Mazières, Liubov Soroka, Ihor Kulai, Andrii Karpus, Dmitry A. Valyaev, Rinaldo Poli, Valérie Bourdon, Eric Manoury, Mathias Destarac, Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Laboratoire de chimie de coordination (LCC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service Commun de Spectrométrie de Masse (Toulouse, France), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ANR-16-CE29-0014,RAFTSWITCH,Agents de Transfert RAFT Modulables pour la Polymérisation Radicalaire Contrôlée.(2016), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), P3R - Polymères de Précision par Procédés Radicalaires (P3R), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)

Subjects
chemistry.chemical_classification, Polymers and Plastics, Diphenylphosphine, Organic Chemistry, chemistry.chemical_element, Infrared spectroscopy, Bioengineering, 02 engineering and technology, Raft, Manganese, Polymer, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Biochemistry, Coupling reaction, 0104 chemical sciences, chemistry.chemical_compound, [CHIM.POLY]Chemical Sciences/Polymers, chemistry, Polymerization, Polymer chemistry, Copolymer, [CHIM.COOR]Chemical Sciences/Coordination chemistry, 0210 nano-technology
Abstract

International audience; A new manganese RAFT agent of the formula Cp(CO)(2)MnP(Ph)(2)C(?S)SCH(CH3)Ph was synthesized in a good overall yield by a three-step reaction from cymantrene and diphenylphosphine as the main starting materials. This complex proved to be efficient for the control of RAFT polymerisation of St, n-BA and DMAAm. The reaction course could be conveniently monitored by P-31 NMR spectroscopy. The controlled character of these polymerisations and the integrity of the polymer chain ends were demonstrated by the synthesis of diblock copolymers of St and n-BA. In the case of long polymerisation times (i.e. for PSt), photo-induced polymer chain coupling reactions were detected. Importantly, removal of the Mn-RAFT--chain end by visible light irradiation led to the formation of a monomodal SH-terminated PSt. These phenomena were evidenced by IR spectroscopy, SEC with RI and UV detection modes and by ESI mass spectrometry.

Published
2019
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14. Synthesis of S-Alkyl Phosphinocarbodithioates with Switch between P(III) and P(V) Derivatives

Author

Eric Manoury, Mathias Destarac, Jean-Claude Daran, Andrii Karpus, Stéphane Mazières, Rinaldo Poli, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Centre National de la Recherche Scientifique (CNRS), ANR-16-CE29-0014,RAFTSWITCH,Agents de Transfert RAFT Modulables pour la Polymérisation Radicalaire Contrôlée.(2016), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), P3R - Polymères de Précision par Procédés Radicalaires (P3R), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT)

Subjects
chemistry.chemical_classification, Resonance structures, 010405 organic chemistry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, Atom (order theory), Reaction products, Phosphorus, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, Crystallography, chemistry, Oxidation state, Mixtures, Salts, Alkyl
Abstract

International audience; Simple and effective synthetic pathways are described to prepare compounds R2P(X)C(S)SCH(Me)Ph with the P atom either in the oxidation state V [R/X = t-Bu/O (6), Ph/S, (7), t-Bu/S (8), t-Bu/Se (9)] or III [R/X = Ph/BH3 (4), t-Bu/BH3 (5), t-Bu/lone pair (10)]. Compound 9 is the first example of carbodithioate ester with a P=Se group and for the first time a phosphinocarboditioate with a free phosphine function (compound 10) is described. Stabilization of the latter crucially depends on the steric protection by the t-Bu groups, since an analogous derivative with R = Ph is observable but too unstable for isolation. Compound 10 can be reversibly protonated to yield the [t-Bu2PHC(S)SCH(Me)Ph] + cation (10-H +), which was isolated as a BF4-salt. A few interconversion processes resulting in the facile addition/removal or exchange of the X group in this family of compounds are also described. The phosphorus atom oxidation state and the nature of electron-withdrawing group have a significant impact on the spectral properties.

Published
2019
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15. Non-invasive intranasal administration route directly to the brain using dendrimer nanoplatforms: An opportunity to develop new CNS drugs

Author

Andrii Karpus, Serge Mignani, Jean-Pierre Majoral, Xiangyang Shi, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centro de Química da Madeira, Universidade da Madeira (UMA), State Key Laboratory for Fiber & Material Modification of Donghua University, Donghua University [Shanghai], Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), PRC NSFC-CNRS 2019, FCT-Fundaçao para a Ciencia e a Tecnologia (Base Fund UIDB/00674/2020 and Programmatic Fund UIDP/00674/2020, Portuguese GovernmentFunds), ARDITI-Agencia Regional para o Desenvolvimento da Investigaçao Tecnologia e Inovaçao - project M1420-01-0145-FEDER-000005-CQMþ (Madeira 14e20 Program), Transnational Euro-NanoMed III - ERANET, and CNRS

Subjects
Calcitonin, Dendrimers, Central nervous system, Review Article, Pharmacology, Macromolecular Compounds, 01 natural sciences, 03 medical and health sciences, Nanocapsules, Intranasal administration, Dendrimer, Drug Discovery, Haloperidol, medicine, Animals, Humans, Insulin, Technology, Pharmaceutical, [CHIM.COOR]Chemical Sciences/Coordination chemistry, RNA, Small Interfering, Dendrimer nanoplatforms, Administration, Intranasal, 030304 developmental biology, 0303 health sciences, Pamam dendrimers, 010405 organic chemistry, Chemistry, Organic Chemistry, Non invasive, Acetophenones, Biological Transport, Dextrans, General Medicine, 3. Good health, 0104 chemical sciences, Drug Liberation, Nose to brain transport pathways, In situ gel formation, medicine.anatomical_structure, Blood-Brain Barrier, Nasal administration, Nanocarriers, Central Nervous System Agents, medicine.drug
Abstract

There are several routes of administration to the brain, including intraparenchymal, intraventricular, and subarachnoid injections. The blood-brain barrier (BBB) impedes the permeation and access of most drugs to the central nervous system (CNS), and consequently, many neurological diseases remain undertreated. For past decades, to circumvent this effect, several nanocarriers have been developed to deliver drugs to the brain. Importantly, intranasal (IN) administration can allow direct delivery of drugs into the brain through the anatomical connection between the nasal cavity and brain without crossing the BBB. In this regard, dendrimers may possess great potential to deliver drugs to the brain by IN administration, bypassing the BBB and reducing systemic exposure and side effects, to treat diseases of the CNS. In this original concise review, we highlighted the few examples advocated regarding the use of dendrimers to deliver CNS drugs directly via IN. This review highlighed the few examples of the association of dendrimer encapsulating drugs (e.g., small compounds: haloperidol and paeonol; macromolecular compounds: dextran, insulin and calcitonin; and siRNA) using IN administration. Good efficiencies were observed. In addition, we will present the in vivo effects of PAMAM dendrimers after IN administration, globally, showing no general toxicity., Graphical abstract Image 1, Highlights • Nose to brain transport pathways. • Nasal route of administration for the treatment of acute and chronic conditions. • Dendrimer platforms as effective nanocarriers to brain. • Nose to brain transport pathways of drugs in association with dendrimers using intranasal administration route. • In vivo neurological effects of nasal exposure of dendrimers.

Published
2021
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16. Chiral Phosphinoferrocenyl-Calixarenes

Author

Jean-Claude Daran, Rinaldo Poli, V. I. Boiko, Andrii Karpus, Eric Manoury, Zoia Voitenko, Vitaly I. Kalchenko, and Oleksandr A. Yesypenko

Subjects
010405 organic chemistry, Organic Chemistry, Enantioselective synthesis, Alkylation, 010402 general chemistry, 01 natural sciences, Medicinal chemistry, Dimethyl malonate, Coupling reaction, 0104 chemical sciences, Catalysis, chemistry.chemical_compound, Tsuji–Trost reaction, chemistry, Calixarene, Organic chemistry, Physical and Theoretical Chemistry, Phosphine
Abstract

The Mitsunobu alkylation of 4-tert-butylcalix[4]arene with (S)-(2-diphenylthiophosphinoferrocenyl)methanol followed by desulfuration of the thiophosphine unit using tris(dimethylamino)phosphine afforded enantiomerically pure calixarene mono- and di(ferrocenylphosphine) ligands in high yields. The calixarene mono(ferrocenylphosphine) ligands exhibited good catalytic activity but low atropoenantioselectivity when used in the asymmetric Suzuki–Miyaura coupling reaction of 1-naphthaleneboronic acid and 1-bromo-2-methylnaphthalene. However, the di(ferrocenylphosphine) ligand displayed both good catalytic activity and enantioselectivity (ee values up to 86 %) when employed in the asymmetric Tsuji–Trost allylic alkylation of 1,3-diphenylprop-2-enyl acetate with dimethyl malonate.

Published
2016
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17. Organocatalytic Michael Addition as a Method for Polyisobutylene Chain‐End Functionalization

Author

Ihor Kulai, David E. Bergbreiter, Hassan S. Bazzi, Mohammed Al-Hashimi, Andrii Karpus, Interactions moléculaires et réactivité chimique et photochimique (IMRCP), Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Fluides, Energie, Réacteurs, Matériaux et Transferts (FERMAT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), P3R - Polymères de Précision par Procédés Radicalaires (P3R), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie de Toulouse (ICT), Laboratoire de chimie de coordination (LCC), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Territoires, Environnement, Télédétection et Information Spatiale (UMR TETIS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-AgroParisTech-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)

Subjects
Polymers and Plastics, Polymers, 02 engineering and technology, Polyenes, 010402 general chemistry, behavioral disciplines and activities, 01 natural sciences, chemistry.chemical_compound, Nucleophile, Thiolactone, Materials Chemistry, [CHIM]Chemical Sciences, Sulfhydryl Compounds, Amines, ComputingMilieux_MISCELLANEOUS, Acrylate, Chemistry, 010405 organic chemistry, Organic Chemistry, Nuclear magnetic resonance spectroscopy, 021001 nanoscience & nanotechnology, Combinatorial chemistry, 0104 chemical sciences, Michael reaction, Click chemistry, Surface modification, 0210 nano-technology, Macromolecule
Abstract

Functionalization of polyolefins, in particular polyisobutylene, remains a relatively unexplored application for the Michael reaction. This work evaluates the potential of polyisobutylene acrylate (PIBA) chain-end modification via organocatalyzed thiol-Michael and aza-Michael additions. A series of chain-end functional polyisobutylene oligomers are prepared using "click" reactions of thiols or amines to PIBA in the presence of 0.02 equivalents of organocatalyst. Reaction kinetics and chain-end transformations are monitored using NMR spectroscopy and the macromolecular products are characterized by size exclusion chromatography. Further potential of this synthetic strategy is illustrated by thiol-Michael addition of thiols formed in situ via nucleophilic thiolactone ring opening. The obtained results provide an efficient method for the preparation of functional polyisobutylene oligomers that can be utilized in a broad range of potential applications.

Published
2020
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18. Synthesis of an enantiomerically pure inherently chiral calix[4]arene phosphonic acid and its evaluation as an organocatalyst

Author

Eric Manoury, V. I. Boiko, Jean-Claude Daran, Oleksandr A. Yesypenko, Andrii Karpus, Vitaly I. Kalchenko, Zoia Voitenko, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), National Taras Shevchenko University of Kiev, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, National Academy of Sciences of Ukraine (NASU), and Institute of Organic Chemistry of NASU [Kyiv]

Subjects
Organophosphorus compounds, Aromatic compounds, 010405 organic chemistry, Organic Chemistry, Epoxide, Reaction products, Molecules, 010402 general chemistry, Inherent chirality, 01 natural sciences, Hydrocarbons, 0104 chemical sciences, Catalysis, chemistry.chemical_compound, chemistry, Organocatalysis, Calixarene, Organic chemistry, [CHIM.COOR]Chemical Sciences/Coordination chemistry, Enantiomer, Brønsted–Lowry acid–base theory, Benzoic acid
Abstract

International audience; A facile method for the preparation of enantiomerically pure inherently chiral calix[4]arene phosphonic acid (cR,pR)-7 in four steps starting from the readily available and previously synthesized (cS)-enantiomer of calix[4]arene acetic acid 1 or its methyl ester 2 was developed. The first tests of this unique calixarene Brönsted acid with inherent chirality in organocatalysis of the aza-Diels–Alder reaction of imines with Danishefsky’s diene and epoxide ring opening by benzoic acid were performed. The calixarene phosphonic acid (cR,pR)-7 shows good catalytic activities but with low enantioselectivities in these reactions.

Published
2018
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19. Stereoselective synthesis of enantiomerically pure inherently chiral p-tert-butylcalix[4]arene carboxylic acids

Author

Oleksandr A. Yesypenko, Sergei G. Garasevich, Andrii Karpus, Vitaly I. Kalchenko, Vyacheslav I. Boyko, Zoia Voitenko, Leonid Andronov, and Alexander N. Chernega

Subjects
Inorganic Chemistry, Chiral auxiliary, chemistry.chemical_compound, Chemistry, Stereochemistry, Organic Chemistry, Diastereomer, Stereoselectivity, Physical and Theoretical Chemistry, Enantiomer, Catalysis
Abstract

Both enantiomers of inherently chiral dipropoxy-p-tert-butylcalix[4]arene carboxylic acids with AABH substitution patterns have been prepared by the stereoselective reactions of 25,26-dipropoxy-p-tert-butylcalix[4]arene with enantiomerically pure (S)- or (R)-N-(1-phenylethyl)bromoacetamide, separation of the diastereomers by recrystallization, and removal of the chiral auxiliary groups. The absolute configurations of the obtained compounds have been established by X-ray analysis.

Published
2012
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20. Synthesis and stereochemical configuration of inherently chiral p-tert-butylcalix[4]arene carboxylic acids and their derivatives

Author

Andrii Karpus, Oleksandr A. Yesypenko, Alexander N. Chernega, Leonid Andronov, Vyacheslav I. Boyko, Vitaly I. Kalchenko, and Zoia Voitenko

Subjects
Chiral auxiliary, chemistry.chemical_compound, Column chromatography, Chemistry, Stereochemistry, Diastereomer, Absolute configuration, Stereoselectivity, General Chemistry, Enantiomer, Condensed Matter Physics, Chiral derivatizing agent, Food Science
Abstract

Both enantiomers of inherently chiral p-tert-butylcalix[4]arene carboxylic acids with ABHH substitution patterns have been prepared by stereoselective reaction of monopropoxy-p-tert-butylcalix[4]arene with an (R)-N-(1-phenylethyl)bromoacetamide, separation of the diastereomers by column chromatography, and removal of the chiral auxiliary groups. The absolute configuration of obtained compounds has been established by X-ray analysis.

Published
2012
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21. New ferrocene derivatives for ligand grafting

Author

Eric Manoury, Andrii Karpus, Jean-Claude Daran, Zoia Voitenko, Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Taras Shevchenko National University of Kyiv

Subjects
Grafting, 010405 organic chemistry, Ligand, chemistry.chemical_element, 010402 general chemistry, Mass spectrometry, 01 natural sciences, Nitrogen, 3. Good health, 0104 chemical sciences, chemistry.chemical_compound, chemistry, Ferrocene, X-ray crystallography, Polymer chemistry, Molecule, Organic chemistry, P N ligands, [CHIM.COOR]Chemical Sciences/Coordination chemistry, P O ligands, Phosphine
Abstract

Five new 1,2-disubstituted ferrocene derivatives have been efficiently synthesized. These compounds contain one protected phosphine function as thiophosphine, another coordination site (nitrogen or oxygen atom) and a function ready for the grafting on various supports. All compounds have been and fully characterized by NMR(1H, 31P and 13C) and High Resolution Mass Spectroscopy. The molecular structure of three of these ferrocene derivatives have been determined by X ray diffraction analysis on monocrystals.

Published
2015
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