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  1. Article ; Online: Polyamine–Drug Conjugates

    Filippo Basagni / Giambattista Marotta / Michela Rosini / Anna Minarini

    Molecules, Vol 28, Iss 4518, p

    Do They Boost Drug Activity?

    2023  Volume 4518

    Abstract: Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological ... ...

    Abstract Over the past two decades, the strategy of conjugating polyamine tails with bioactive molecules such as anticancer and antimicrobial agents, as well as antioxidant and neuroprotective scaffolds, has been widely exploited to enhance their pharmacological profile. Polyamine transport is elevated in many pathological conditions, suggesting that the polyamine portion could improve cellular and subcellular uptake of the conjugate via the polyamine transporter system. In this review, we have presented a glimpse on the polyamine conjugate scenario, classified by therapeutic area, of the last decade with the aim of highlighting achievements and fostering future developments.
    Keywords polyamine ; drug conjugate ; antitumor ; antimicrobial ; neuroprotective ; Organic chemistry ; QD241-441
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Memantine Derivatives as Multitarget Agents in Alzheimer’s Disease

    Giambattista Marotta / Filippo Basagni / Michela Rosini / Anna Minarini

    Molecules, Vol 25, Iss 4005, p

    2020  Volume 4005

    Abstract: Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer’s disease (AD), a neurodegenerative condition characterized by a ... ...

    Abstract Memantine (3,5-dimethyladamantan-1-amine) is an orally active, noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist approved for treatment of moderate-to-severe Alzheimer’s disease (AD), a neurodegenerative condition characterized by a progressive cognitive decline. Unfortunately, memantine as well as the other class of drugs licensed for AD treatment acting as acetylcholinesterase inhibitors (AChEIs), provide only symptomatic relief. Thus, the urgent need in AD drug development is for disease-modifying therapies that may require approaching targets from more than one path at once or multiple targets simultaneously. Indeed, increasing evidence suggests that the modulation of a single neurotransmitter system represents a reductive approach to face the complexity of AD. Memantine is viewed as a privileged NMDAR-directed structure, and therefore, represents the driving motif in the design of a variety of multi-target directed ligands (MTDLs). In this review, we present selected examples of small molecules recently designed as MTDLs to contrast AD, by combining in a single entity the amantadine core of memantine with the pharmacophoric features of known neuroprotectants, such as antioxidant agents, AChEIs and Aβ-aggregation inhibitors.
    Keywords memantine ; Alzheimer’s disease ; multi target directed ligand ; hybrid structures ; Organic chemistry ; QD241-441
    Subject code 004
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Double Attack to Oxidative Stress in Neurodegenerative Disorders

    Filippo Basagni / Maria Luisa Di Paolo / Giorgio Cozza / Lisa Dalla Via / Francesca Fagiani / Cristina Lanni / Michela Rosini / Anna Minarini

    Molecules, Vol 28, Iss 21, p

    MAO-B and Nrf2 as Elected Targets

    2023  Volume 7424

    Abstract: Oxidative stress and neuroinflammation play a pivotal role in triggering the neurodegenerative pathological cascades which characterize neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. In search for potential efficient ... ...

    Abstract Oxidative stress and neuroinflammation play a pivotal role in triggering the neurodegenerative pathological cascades which characterize neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. In search for potential efficient treatments for these pathologies, that are still considered unmet medical needs, we started from the promising properties of the antidiabetic drug pioglitazone, which has been repositioned as an MAO-B inhibitor, characterized by promising neuroprotective properties. Herein, with the aim to broaden its neuroprotective profile, we tried to enrich pioglitazone with direct and indirect antioxidant properties by hanging polyphenolic and electrophilic features that are able to trigger Nrf2 pathway and the resulting cytoprotective genes’ transcription, as well as serve as radical scavengers. After a preliminary screening on MAO-B inhibitory properties, caffeic acid derivative 2 emerged as the best inhibitor for potency and selectivity over MAO-A, characterized by a reversible mechanism of inhibition. Furthermore, the same compound proved to activate Nrf2 pathway by potently increasing Nrf2 nuclear translocation and strongly reducing ROS content, both in physiological and stressed conditions. Although further biological investigations are required to fully clarify its neuroprotective properties, we were able to endow the pioglitazone scaffold with potent antioxidant properties, representing the starting point for potential future pioglitazone-based therapeutics for neurodegenerative disorders.
    Keywords pioglitazone ; MAO-B ; Nrf2 ; electrophile ; cinnamic acid ; oxidative stress ; Organic chemistry ; QD241-441
    Subject code 540
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article: Natural polyamines and synthetic analogs modify the growth and the morphology of Pyrus communis pollen tubes affecting ROS levels and causing cell death

    Aloisi, Iris / Anna Minarini / Giampiero Cai / Stefano Del Duca / Vincenzo Tumiatti

    Plant science. 2015 Oct., v. 239

    2015  

    Abstract: Polyamines (PAs) are small molecules necessary for pollen maturation and tube growth. Their role is often controversial, since they may act as pro-survival factors as well as factors promoting Programmed Cell Death (PCD). The aim of the present work was ... ...

    Abstract Polyamines (PAs) are small molecules necessary for pollen maturation and tube growth. Their role is often controversial, since they may act as pro-survival factors as well as factors promoting Programmed Cell Death (PCD). The aim of the present work was to evaluate the effect of exogenous PAs on the apical growth of pear (Pyrus communis) pollen tube and to understand if PAs and reactive oxygen species (ROS) are interconnected in the process of tip-growth. In the present study besides natural PAs, also aryl-substituted spermine and methoctramine (Met 6-8-6) analogs were tested. Among the natural PAs, Spm showed strongest effects on tube growth. Spm entered through the pollen tube tip, then diffused in the sub-apical region that underwent drastic morphological changes, showing enlarged tip. Analogs were mostly less efficient than natural PAs but BD23, an asymmetric synthetic PAs bearing a pyridine ring, showed similar effects. These effects were related to the ability of PAs to cause the decrease of ROS level in the apical zone, leading to cell death, counteracted by the caspase-3 inhibitor Ac-DEVD-CHO (DEVD). In conclusions, ROS are essential for pollen germination and a strict correlation between ROS regulation and PA concentration is reported. Moreover, an imbalance between ROS and PAs can be detrimental thereby driving pollen toward cell death.
    Keywords apoptosis ; caspase-3 ; pears ; pollen ; pollen tubes ; pyridines ; Pyrus communis ; reactive oxygen species ; spermine
    Language English
    Dates of publication 2015-10
    Size p. 92-105.
    Publishing place Elsevier Ireland Ltd
    Document type Article
    ZDB-ID 742010-9
    ISSN 1873-2259 ; 0168-9452
    ISSN (online) 1873-2259
    ISSN 0168-9452
    DOI 10.1016/j.plantsci.2015.07.008
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

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  5. Article ; Online: Study of the Cytotoxic Effects of the New Synthetic Isothiocyanate CM9 and Its Fullerene Derivative on Human T-Leukemia Cells

    Elena De Gianni / Eleonora Turrini / Andrea Milelli / Francesca Maffei / Marco Carini / Anna Minarini / Vincenzo Tumiatti / Tatiana Da Ros / Maurizio Prato / Carmela Fimognari

    Toxins, Vol 7, Iss 2, Pp 535-

    2015  Volume 552

    Abstract: One important strategy to develop effective anticancer agents is based on natural products. Many active phytochemicals are in human clinical trials and have been used for a long time, alone and in association with conventional anticancer drugs, for the ... ...

    Abstract One important strategy to develop effective anticancer agents is based on natural products. Many active phytochemicals are in human clinical trials and have been used for a long time, alone and in association with conventional anticancer drugs, for the treatment of various types of cancers. A great number of in vitro, in vivo and clinical reports document the multi-target anticancer activities of isothiocyanates and of compounds characterized by a naphthalenetetracarboxylic diimide scaffold. In order to search for new anticancer agents with a better pharmaco-toxicological profile, we investigated hybrid compounds obtained by inserting isothiocyanate group(s) on a naphthalenetetracarboxylic diimide scaffold. Moreover, since water-soluble fullerene derivatives can cross cell membranes thus favoring the delivery of anticancer therapeutics, we explored the cytostatic and cytotoxic activity of hybrid compounds conjugated with fullerene. We studied their cytostatic and cytotoxic effects on a human T-lymphoblastoid cell line by using different flow cytometric assays. In order to better understand their pharmaco-toxicological potential, we also analyzed their genotoxicity. Our global results show that the synthesized compounds reduced significantly the viability of leukemia cells. However, the conjugation with a non-toxic vector did not increase their anticancer potential. This opens an interesting research pattern for certain fullerene properties.
    Keywords fullerene ; isothiocyanate ; naphthalene diimide ; cancer ; apoptosis ; cell proliferation ; p53 ; doxorubicin ; genotoxicity ; Medicine ; R
    Subject code 500
    Language English
    Publishing date 2015-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Tumor vascular targeted liposomal-bortezomib minimizes side effects and increases therapeutic activity in human neuroblastoma

    Zuccari, Guendalina / Amelia Parise / Andrea Milelli / Andrea Petretto / Anna Minarini / Chiara Brignole / Chiara Marchetti / Daniela Di Paolo / Fabio Pastorino / Francesca Piaggio / Gabriella Pagnan / Laura Emionite / Michele Cilli / Mirco Ponzoni / Monica Loi / Patrizia Perri / Vincenzo Tumiatti / Vito Pistoia

    Journal of controlled release. 2015 Aug. 10, v. 211

    2015  

    Abstract: Neuroblastoma is a childhood cancer with poor long-term prognosis in advanced stages. A major aim in neuroblastoma therapy is to develop targeted drug delivery systems to ameliorate drug therapeutic index and efficacy. In this study, a novel bortezomib ( ... ...

    Abstract Neuroblastoma is a childhood cancer with poor long-term prognosis in advanced stages. A major aim in neuroblastoma therapy is to develop targeted drug delivery systems to ameliorate drug therapeutic index and efficacy. In this study, a novel bortezomib (BTZ) liposomal formulation was set-up and characterized. Since BTZ is freely permeable across the lipidic bilayer, an amino-lactose (LM) was synthesized as complexing agent to entrap BTZ inside the internal aqueous compartment of stealth liposomes. High encapsulation efficiency was achieved by a loading method based on the formation of boronic esters between the boronic acid moiety of BTZ and the hydroxyl groups of LM. Next, NGR peptides were linked to the liposome surface as a targeting-ligand for the tumor endothelial cell marker, aminopeptidase N. Liposomes were characterized for size, Z-potential, polydispersity index, drug content, and release. Lyophilization in the presence of cryoprotectants (trehalose, sucrose) was also examined in terms of particle size changes and drug leakage.BTZ was successfully loaded into non-targeted (SL[LM-BTZ]) and targeted (NGR-SL[LM-BTZ]) liposomes with an entrapment efficiency of about 68% and 57%, respectively. These nanoparticles were suitable for intravenous administration, presenting an average diameter of 170nm and narrow polydispersity. Therefore, orthotopic NB-bearing mice were treated with 1.0 or 1.5mg/kg of BTZ, either in free form or encapsulated into liposomes. BTZ loaded liposomes showed a significant reduction of drug systemic adverse effects with respect to free drug, even at the highest dose tested. Moreover, mice treated with 1.5mg/kg of NGR-SL[LM-BTZ] lived statistically longer than untreated mice (P=0.0018) and SL[LM-BTZ]-treated mice (P=0.0256). Our results demonstrate that the novel vascular targeted BTZ formulation is endowed with high therapeutic index and low toxicity, providing a new tool for future applications in neuroblastoma clinical studies.
    Keywords adverse effects ; childhood ; clinical trials ; cryoprotectants ; drug delivery systems ; drugs ; encapsulation ; endothelial cells ; esters ; freeze drying ; humans ; intravenous injection ; membrane alanyl aminopeptidase ; mice ; moieties ; nanoparticles ; neoplasms ; particle size ; peptides ; prognosis ; sucrose ; toxicity ; trehalose
    Language English
    Dates of publication 2015-0810
    Size p. 44-52.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2015.05.286
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

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