LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 69

Search options

  1. Article ; Online: The Quest for Secondary Pharmaceuticals: Drug Repurposing/Chiral-Switches Combination Strategy.

    D'Acquarica, Ilaria / Agranat, Israel

    ACS pharmacology & translational science

    2023  Volume 6, Issue 2, Page(s) 201–219

    Abstract: Drug repurposing toward new medical uses and chiral switches are elements of secondary pharmaceuticals. The drug repurposing and chiral-switches strategies have mostly been applied independently in drug discovery. Drug repurposing has peaked in the ... ...

    Abstract Drug repurposing toward new medical uses and chiral switches are elements of secondary pharmaceuticals. The drug repurposing and chiral-switches strategies have mostly been applied independently in drug discovery. Drug repurposing has peaked in the search for therapeutic treatments of the Coronavirus Disease 2019 pandemic, whereas chiral switches have been overlooked. The current Perspective introduces the drug repurposing/chiral-switches combination strategy, overviewing representative cases of chiral drugs that have undergone this combination: ketamine, flurbiprofen, fenfluramine, and milnacipran. The deuterium-enabled chiral switches of racemic thalidomide analogs, a variation of the repurposing/chiral-switch combination strategy, is also included. Patenting and regulatory-exclusivity considerations of the combination strategy in the discovery of new medical uses are considered. The proposed combination creates a new synergy of its two elements, overcoming arguments against chiral switches, with better prospects for validation of patents and regulatory exclusivities. The combination strategy may be applied to chiral switches to paired enantiomers. Repurposing/chiral-switch drugs may be 'obvious-to-try'; however, their inventions may be unexpected and their patents nonobvious. Patenting repurposing/chiral-switch combination drugs is not 'evergreening', 'product hopping', and 'me-too'. The expected benefits and opportunities of the combined repurposing/chiral-switch strategy vis-à-vis its two elements are superior pharmacological properties, overcoming arguments against patent validities, challenges of chiral-switch patents, reduced expenses, shortened approval procedures, and higher expectations of regulatory exclusivities.
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2575-9108
    ISSN (online) 2575-9108
    DOI 10.1021/acsptsci.2c00151
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Chiral switches of chloroquine and hydroxychloroquine: potential drugs to treat COVID-19.

    D'Acquarica, Ilaria / Agranat, Israel

    Drug discovery today

    2020  Volume 25, Issue 7, Page(s) 1121–1123

    MeSH term(s) Betacoronavirus ; COVID-19 ; Chloroquine/therapeutic use ; Coronavirus Infections/drug therapy ; Drug Repositioning ; Humans ; Hydroxychloroquine/therapeutic use ; Pandemics ; Pneumonia, Viral/drug therapy ; SARS-CoV-2 ; Stereoisomerism
    Chemical Substances Hydroxychloroquine (4QWG6N8QKH) ; Chloroquine (886U3H6UFF)
    Keywords covid19
    Language English
    Publishing date 2020-05-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2020.04.021
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4725: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Chiral distinction between hydroxychloroquine enantiomers in binding to angiotensin-converting enzyme 2, the forward receptor of SARS-CoV-2.

    Aiello, Federica / Balzano, Federica / Uccello Barretta, Gloria / D'Acquarica, Ilaria / Mazzoccanti, Giulia / Agranat, Israel

    Journal of pharmaceutical and biomedical analysis

    2023  Volume 237, Page(s) 115770

    Abstract: Soon after the outset of the Coronavirus Disease 2019 (COVID-19) pandemic (March-April 2020), formulations of the old antimalarial racemic drug hydroxychloroquine (HCQ) sulfate were authorized by the U.S. Food and Drug Administration (FDA) for emergency ... ...

    Abstract Soon after the outset of the Coronavirus Disease 2019 (COVID-19) pandemic (March-April 2020), formulations of the old antimalarial racemic drug hydroxychloroquine (HCQ) sulfate were authorized by the U.S. Food and Drug Administration (FDA) for emergency treatment of hospitalized patients with COVID-19. A call for the chiral switch of HCQ to the single enantiomer (S)-(+)-HCQ for treating the disease followed. The above authorizations were later withdrawn. Angiotensin-converting enzyme 2 (ACE2) has been recognized to be the forward receptor of SARS-CoV-2, the virus responsible for COVID-19. The objective of the present study was to evaluate the chiral distinction in the potential preferential binding of the HCQ enantiomers to ACE2, as a basis for its future drug repurposing, using high-field solution Nuclear Magnetic Resonance (NMR) spectroscopy. Proton selective spin-lattice relaxation rates were measured for selected diagnostic nuclei; in particular, protons belonging to the quinoline ring proved to be the most affected by the presence of the protein, for both (S)-(+)-HCQ and (R)-(-)-HCQ enantiomers. An increase in mono-selective relaxation rates was observed for both enantiomers. A significant difference in the magnitude of the increase was detected for all protons investigated, up to a 5-fold and an 8-fold increase in the case of (R)-(-)-HCQ and (S)-(+)-HCQ, respectively. Furthermore, comparison between the normalized mono-selective relaxation rates of the two HCQ enantiomers in their binary mixtures with ACE2 pointed out a certain preference for the (S)-(+)-HCQ enantiomer over (R)-(-)-HCQ in the interaction with ACE2. The findings form the basis for a future application of the drug repurposing/chiral-switch combination strategy to racemic HCQ in previously reported indications for hydroxychloroquine treatment and in the search for new indications in which ACE2 receptors are involved.
    MeSH term(s) Humans ; Hydroxychloroquine ; SARS-CoV-2 ; COVID-19 ; Angiotensin-Converting Enzyme 2 ; Protons ; COVID-19 Drug Treatment ; Antimalarials/therapeutic use
    Chemical Substances Hydroxychloroquine (4QWG6N8QKH) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Protons ; Antimalarials
    Language English
    Publishing date 2023-10-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2023.115770
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1850: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: Chiral switches of chloroquine and hydroxychloroquine

    D’Acquarica, Ilaria / Agranat, Israel

    Drug Discovery Today

    potential drugs to treat COVID-19

    2020  Volume 25, Issue 7, Page(s) 1121–1123

    Keywords Pharmacology ; Drug Discovery ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2020.04.021
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4725: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: The market of chiral drugs: Chiral switches versus de novo enantiomerically pure compounds.

    Calcaterra, Andrea / D'Acquarica, Ilaria

    Journal of pharmaceutical and biomedical analysis

    2018  Volume 147, Page(s) 323–340

    Abstract: This review article is aimed at providing an overview of the current market of chiral drugs by exploring which is the nowadays tendency, for the pharmaceutical industry, either to exploit the chiral switching practice from already marketed racemates or ... ...

    Abstract This review article is aimed at providing an overview of the current market of chiral drugs by exploring which is the nowadays tendency, for the pharmaceutical industry, either to exploit the chiral switching practice from already marketed racemates or to develop de novo enantiomerically pure compounds. A concise illustration of the main techniques developed to assess the absolute configuration (AC) and enantiomeric purity of chiral drugs has been given, where greater emphasis was placed on the contribution of enantioselective chromatography (HPLC, SFC and UHPC). Afterwards, we focused our study on the cohort of 45 new drugs that have been approved by the US Food and Drug Administration (FDA) in 2015. We extracted the chemical structure of the new drugs from the FDA approval chemistry reviews available on the database of the agency's Center for Drug Evaluation and Research (CDER), and we selected a subgroup (i.e., 44% of the cohort) of small-molecule active pharmaceutical ingredients (APIs) containing one or more chirality centers. On the basis of the FDA dossiers examined, it emerged that all the chiral drugs approved by the FDA in 2015 are enantiomerically pure compounds with a well-defined AC, with the exception of one, namely lesinurad, which has been licensed as the racemate of two enantiomeric atropoisomers, arising because of the hindered rotation around the single C-N bond in the naphthalene ring. Finally, none of the previously developed racemates has been switched to the single-enantiomer version in 2015.
    MeSH term(s) Animals ; Chemistry, Pharmaceutical/economics ; Chemistry, Pharmaceutical/methods ; Chemistry, Pharmaceutical/trends ; Drug Design ; Drug Industry/economics ; Drug Industry/methods ; Drug Industry/trends ; Humans ; Marketing/economics ; Marketing/methods ; Marketing/trends ; Pharmaceutical Preparations/chemistry ; Pharmaceutical Preparations/economics ; Stereoisomerism
    Chemical Substances Pharmaceutical Preparations
    Language English
    Publishing date 2018-01-05
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 604917-5
    ISSN 1873-264X ; 0731-7085
    ISSN (online) 1873-264X
    ISSN 0731-7085
    DOI 10.1016/j.jpba.2017.07.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1850: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Chiral switches of chloroquine and hydroxychloroquine

    D’Acquarica, Ilaria / Agranat, Israel

    potential drugs to treat COVID-19

    2020  

    Abstract: Therapeutic options in response to the COVID-19 pandemic are urgently needed. A keyword in these worldwide effortsis ‘repurposing’ – the development of approved antiviral drugs as candidates for COVID-19. Chloroquine (CQ) and its hydroxyl analog ... ...

    Abstract Therapeutic options in response to the COVID-19 pandemic are urgently needed. A keyword in these worldwide effortsis ‘repurposing’ – the development of approved antiviral drugs as candidates for COVID-19. Chloroquine (CQ) and its hydroxyl analog hydroxychloroquine (HCQ) are showing preliminary inhibitory effects against COVID-19 and apparent efficacy in clinical studies. We propose a variant of the repurposing strategy: developing single enantiomers of these old racemic drugs. We call for urgently pursuing the chiral switches of HCQ and/or CQ for the treatment of COVID-19.
    Keywords COVID-19 ; chiral switch ; hydroxychloroquine ; repurposing strategy ; covid19
    Language English
    Publisher Elsevier B.V.
    Publishing country it
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  8. Article ; Online: Green Routes for the Production of Enantiopure Benzylisoquinoline Alkaloids.

    Ghirga, Francesca / Bonamore, Alessandra / Calisti, Lorenzo / D'Acquarica, Ilaria / Mori, Mattia / Botta, Bruno / Boffi, Alberto / Macone, Alberto

    International journal of molecular sciences

    2017  Volume 18, Issue 11

    Abstract: Benzylisoquinoline alkaloids (BIAs) are among the most important plant secondary metabolites, in that they include a number of biologically active substances widely employed as pharmaceuticals. Isolation of BIAs from their natural sources is an expensive ...

    Abstract Benzylisoquinoline alkaloids (BIAs) are among the most important plant secondary metabolites, in that they include a number of biologically active substances widely employed as pharmaceuticals. Isolation of BIAs from their natural sources is an expensive and time-consuming procedure as they accumulate in very low levels in plant. Moreover, total synthesis is challenging due to the presence of stereogenic centers. In view of these considerations, green and scalable methods for BIA synthesis using fully enzymatic approaches are getting more and more attention. The aim of this paper is to review fully enzymatic strategies for producing the benzylisoquinoline central precursor, (
    MeSH term(s) Alkaloids/chemical synthesis ; Alkaloids/chemistry ; Alkaloids/metabolism ; Bacteria/chemistry ; Bacteria/enzymology ; Bacteria/genetics ; Benzylisoquinolines/chemical synthesis ; Benzylisoquinolines/chemistry ; Benzylisoquinolines/metabolism ; Bioreactors ; Escherichia coli/enzymology ; Escherichia coli/genetics ; Plants/chemistry ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Saccharomyces cerevisiae/enzymology ; Saccharomyces cerevisiae/genetics ; Tetrahydroisoquinolines/chemical synthesis ; Tetrahydroisoquinolines/chemistry ; Tetrahydroisoquinolines/metabolism
    Chemical Substances Alkaloids ; Benzylisoquinolines ; Recombinant Proteins ; Tetrahydroisoquinolines ; higenamine (TBV5O16GAP)
    Language English
    Publishing date 2017-11-20
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms18112464
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: Synthesis of Bromoundecyl Resorc[4]arenes and Applications of the Cone Stereoisomer as Selector for Liquid Chromatography.

    Corradi, Silvia / Mazzoccanti, Giulia / Ghirga, Francesca / Quaglio, Deborah / Nevola, Laura / Massera, Chiara / Ugozzoli, Franco / Giannini, Giuseppe / Ciogli, Alessia / D'Acquarica, Ilaria

    The Journal of organic chemistry

    2018  Volume 83, Issue 15, Page(s) 7683–7693

    Abstract: As an extension of our studies on the multifaceted properties of C-alkylated resorc[4]arenes, we planned to immobilize on a solid support resorc[4]arenes with ... ...

    Abstract As an extension of our studies on the multifaceted properties of C-alkylated resorc[4]arenes, we planned to immobilize on a solid support resorc[4]arenes with C
    Language English
    Publishing date 2018-06-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 123490-0
    ISSN 1520-6904 ; 0022-3263
    ISSN (online) 1520-6904
    ISSN 0022-3263
    DOI 10.1021/acs.joc.8b00488
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4473: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: Total Synthesis of (±)-Kuwanol E.

    Iovine, Valentina / Benni, Irene / Sabia, Rocchina / D'Acquarica, Ilaria / Fabrizi, Giancarlo / Botta, Bruno / Calcaterra, Andrea

    Journal of natural products

    2016  Volume 79, Issue 10, Page(s) 2495–2503

    Abstract: The total synthesis of the Diels-Alder-type adducts (±)-kuwanol E and the heptamethyl ether derivative of (±)-kuwanon Y has been accomplished via a convergent strategy involving 2'-hydroxychalcone 6 or 9 and dehydroprenylstilbene 7, in nine steps. The ... ...

    Abstract The total synthesis of the Diels-Alder-type adducts (±)-kuwanol E and the heptamethyl ether derivative of (±)-kuwanon Y has been accomplished via a convergent strategy involving 2'-hydroxychalcone 6 or 9 and dehydroprenylstilbene 7, in nine steps. The synthesis features, as a key step, a Lewis acid-mediated biomimetic intermolecular Diels-Alder [4+2] cycloaddition for the construction of the cyclohexene skeleton with three stereogenic centers. Notably, the endo/exo diastereoselectivity of the reaction proved to be temperature-controlled.
    MeSH term(s) Chalcones ; Cyclohexenes ; Flavonoids/chemical synthesis ; Flavonoids/chemistry ; Models, Molecular ; Molecular Structure ; Stereoisomerism ; Temperature
    Chemical Substances Chalcones ; Cyclohexenes ; Flavonoids ; kuwanol E ; cyclohexene (12L0P8F7GN) ; 2'-hydroxychalcone (VY06DZ94OC)
    Language English
    Publishing date 2016-10-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 304325-3
    ISSN 1520-6025 ; 0163-3864
    ISSN (online) 1520-6025
    ISSN 0163-3864
    DOI 10.1021/acs.jnatprod.6b00350
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1144: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top