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  1. Article ; Online: Isomers Recognition in HPLC-MS/MS Analysis of Human Plasma Samples by Using an Ion Trap Supported by a Linear Equations-Based Algorithm

    Marco Pallecchi / Luigi Lucio / Laura Braconi / Marta Menicatti / Silvia Dei / Elisabetta Teodori / Gianluca Bartolucci

    International Journal of Molecular Sciences, Vol 24, Iss 11155, p

    2023  Volume 11155

    Abstract: The tandem mass spectrometry (MS/MS) approach employing an ion trap mass analyzer (IT) was evaluated in isomers recognition. The proposed approach consists of sole, simple, and rapid liquid chromatographic separation (HPLC) without requiring resolution ... ...

    Abstract The tandem mass spectrometry (MS/MS) approach employing an ion trap mass analyzer (IT) was evaluated in isomers recognition. The proposed approach consists of sole, simple, and rapid liquid chromatographic separation (HPLC) without requiring resolution between the analytes. Then, the MS/MS properties were optimized to solve the signal assignment using post-processing data elaboration (LEDA). The IT-MS/MS experiment uses the same site, helium as collision gas, and different time steps to modify the applied conditions on the studied ions. Nevertheless, helium cannot ensure the quick energization of the precursor ion due to its small cross-section. Then, different combinations between excitation amplitude (ExA) and excitation time (ExT) were tested to achieve the activation of the fragmentation channels and the formation of the MS/MS spectrum. Usually, the IT-MS/MS acquisition cycle is longer for other multistage instruments, decreasing the frequency of sample data collection and influencing the chromatographic profile. To solve these problems, two time segments were set up, and the elution conditions were optimized with a compromise between peaks distinction and run time reduction. The developed HPLC-MS/MS method was checked and applied to analyze a series of human plasma samples spiked with an equimolar mixture of pair of isomers.
    Keywords ion trap ; ERMS ; breakdown curves ; collision energy ; enzymatic degradation kinetics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Simultaneous Degradation Study of Isomers in Human Plasma by HPLC-MS/MS and Application of LEDA Algorithm for Their Characterization

    Marco Pallecchi / Laura Braconi / Marta Menicatti / Sara Giachetti / Silvia Dei / Elisabetta Teodori / Gianluca Bartolucci

    International Journal of Molecular Sciences, Vol 23, Iss 13139, p

    2022  Volume 13139

    Abstract: This paper proposes a tandem mass spectrometry (MS/MS) approach in isomer recognition by playing in the “energetic dimension” of the experiment. The chromatographic set up (HPLC) was tuned to minimize the run time, without requiring high efficiency or ... ...

    Abstract This paper proposes a tandem mass spectrometry (MS/MS) approach in isomer recognition by playing in the “energetic dimension” of the experiment. The chromatographic set up (HPLC) was tuned to minimize the run time, without requiring high efficiency or resolution between the isomers. Then, the MS/MS properties were explored to solve the signal assignment by performing a series of energy resolved experiments in order to optimize the parameters, and by applying an interesting post-processing data elaboration tool (LEDA). The reliability of the new approach was evaluated, determining the accuracy and precision of the quantitative results through analysis of the isomer mixture solutions. Next, the proposed method was applied in a chemical stability study of human plasma samples through the simultaneous addition of a pair of isomers. In the studied case, only one of the isomers suffered of enzymatic hydrolysis; therefore, the influence of the stable isomer on the degradation rate of the other was verified. In order to monitor this process correctly, it must be possible to distinguish each isomer present in the sample, quantify it, and plot its degradation profile. The reported results demonstrated the effectiveness of the LEDA algorithm in separating the isomers, without chromatographic resolution, and monitoring their behavior in human plasma samples.
    Keywords triple quadrupole system ; ERMS ; breakdown curves ; collision energy ; enzymatic degradation kinetics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 660
    Language English
    Publishing date 2022-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Mass Spectrometry Study about In Vitro and In Vivo Reaction between Metformin and Glucose

    Gianluca Bartolucci / Marco Pallecchi / Laura Braconi / Silvia Dei / Elisabetta Teodori / Annunziata Lapolla / Giovanni Sartore / Pietro Traldi

    International Journal of Molecular Sciences, Vol 25, Iss 1, p

    A Preliminary Investigation on Alternative Biological Behavior

    2023  Volume 180

    Abstract: Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are prescribed this drug annually. Some different action mechanisms have been proposed for this drug, but, surprisingly, no metabolite of metformin has ... ...

    Abstract Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are prescribed this drug annually. Some different action mechanisms have been proposed for this drug, but, surprisingly, no metabolite of metformin has ever been described. It was considered interesting to investigate the possible reaction of metformin with glucose following the Maillard reaction pattern. The reaction was first performed in in vitro conditions, showing the formation of two adducts that originated by the condensation of the two molecular species with the losses of one or two water molecules. Their structures were investigated by liquid chromatography coupled with mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS) and accurate mass measurements (HRMS). The species originated via the reaction of glucose and metformin and were called metformose and dehydrometformose , and some structural hypotheses were conducted. It is worth to emphasize that they were detected in urine samples from a diabetic patient treated with metformin and consequently they must be considered metabolites of the drug, which has never been identified before now. The glucose-related substructure of these compounds could reflect an improved transfer across cell membranes and, consequently, new hypotheses could be made about the biological targets of metformin.
    Keywords metformin ; reaction of metformin with glucose ; mass spectrometry ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Aromatic Sulfonamides including a Sulfonic Acid Tail

    Simone Giovannuzzi / Mario D’Ambrosio / Cristina Luceri / Sameh Mohamed Osman / Marco Pallecchi / Gianluca Bartolucci / Alessio Nocentini / Claudiu T. Supuran

    International Journal of Molecular Sciences, Vol 23, Iss 461, p

    New Membrane Impermeant Carbonic Anhydrase Inhibitors for Targeting Selectively the Cancer-Associated Isoforms

    2022  Volume 461

    Abstract: We report here a new drug design strategy for producing membrane-impermeant carbonic anhydrase (CA; EC 4.2.1.1) inhibitors selectively targeting the tumor-associated, membrane-bound human CAs IX and XII over off-target cytosolic isoforms. To date, this ... ...

    Abstract We report here a new drug design strategy for producing membrane-impermeant carbonic anhydrase (CA; EC 4.2.1.1) inhibitors selectively targeting the tumor-associated, membrane-bound human CAs IX and XII over off-target cytosolic isoforms. To date, this approach has only been pursued by including permanent positively charged pyridinium type or highly hydrophilic glycosidic moieties into the structure of aromatic sulfonamide CA inhibitors (CAIs). Aliphatic (propyl and butyl) sulfonic acid tails, deprotonated at physiological pH, were thus incorporated onto a benzenesulfonamide scaffold by a common 1,2,3-triazole linker and different types of spacers. Twenty such derivatives were synthesized and tested for their inhibition of target (hCAs IV, IX, and XII) and off-target CAs (hCAs I and II). Most sulfonate CAIs induced a potent inhibition of hCAs II, IX, and XII up to a low nanomolar K I range (0.9–459.4 nM) with a limited target/off-target CA selectivity of action. According to the drug design schedule, a subset of representative derivatives was assessed for their cell membrane permeability using Caco-2 cells and a developed FIA-MS/MS method. The complete membrane impermeability of the sulfonate tailed CAIs (≥98%) validated these negatively charged moieties as being suitable for achieving, in vivo, the selective targeting of the tumor-associated CAs over off-target ones.
    Keywords carbonic anhydrase ; cancer ; membrane-impermeability ; inhibition ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Design, Synthesis and Pharmacological Evaluation of New Quinoline-Based Panx-1 Channel Blockers

    Letizia Crocetti / Maria Paola Giovannoni / Gabriella Guerrini / Silvia Lamanna / Fabrizio Melani / Gianluca Bartolucci / Marco Pallecchi / Paola Paoli / Martina Lippi / Junjie Wang / Gerhard Dahl

    International Journal of Molecular Sciences, Vol 24, Iss 2022, p

    2023  Volume 2022

    Abstract: Pannexins are an interesting new target in medicinal chemistry, as they are involved in many pathologies such as epilepsy, ischemic stroke, cancer and Parkinson’s disease, as well as in neuropathic pain. They are a family of membrane channel proteins ... ...

    Abstract Pannexins are an interesting new target in medicinal chemistry, as they are involved in many pathologies such as epilepsy, ischemic stroke, cancer and Parkinson’s disease, as well as in neuropathic pain. They are a family of membrane channel proteins consisting of three members, Panx-1, Panx-2 and Panx-3, and are expressed in vertebrates. In the present study, as a continuation of our research in this field, we report the design, synthesis and pharmacological evaluation of new quinoline-based Panx-1 blockers. The most relevant compounds 6f and 6g show an IC 50 = 3 and 1.5 µM, respectively, and are selective Panx-1 blockers. Finally, chemical stability, molecular modelling and X-ray crystallography studies have been performed providing useful information for the realization of the project.
    Keywords pannexins ; panx-1 blockers ; quinolones ; quinolines ; molecular modeling ; chemical stability ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article: Characterization of the "gut microbiota-immunity axis" and microbial lipid metabolites in atrophic and potential celiac disease.

    Federica, Ricci / Edda, Russo / Daniela, Renzi / Simone, Baldi / Giulia, Nannini / Gabriele, Lami / Marta, Menicatti / Marco, Pallecchi / Gianluca, Bartolucci / Elena, Niccolai / Matteo, Cerboneschi / Serena, Smeazzetto / Matteo, Ramazzotti / Amedeo, Amedei / Salvatore, Calabrò Antonino

    Frontiers in microbiology

    2022  Volume 13, Page(s) 886008

    Abstract: Introduction: Potential celiac disease (pCD) is characterized by genetic predisposition, positive anti-endomysial and anti-tissue transglutaminase antibodies, but a normal or almost normal jejunal mucosa (e.g., minor histological abnormalities without ... ...

    Abstract Introduction: Potential celiac disease (pCD) is characterized by genetic predisposition, positive anti-endomysial and anti-tissue transglutaminase antibodies, but a normal or almost normal jejunal mucosa (e.g., minor histological abnormalities without villous atrophy). To gain further insights into basic mechanisms involved in the development of intestinal villous atrophy, we evaluated and compared the microbial, lipid, and immunological signatures of pCD and atrophic CD (aCD).
    Materials and methods: This study included 17 aCD patients, 10 pCD patients, and 12 healthy controls (HC). Serum samples from all participants were collected to analyze free fatty acids (FFAs). Duodenal mucosa samples of aCD and pCD patients were taken to evaluate histology, tissue microbiota composition, and mucosal immune response.
    Results: We found no significant differences in the mucosa-associated microbiota composition of pCD and aCD patients. On the other hand, in pCD patients, the overall abundance of serum FFAs showed relevant and significant differences in comparison with aCD patients and HC. In detail, compared to HC, pCD patients displayed higher levels of propionic, butyric, valeric, 2-ethylhexanoic, tetradecanoic, hexadecanoic, and octadecanoic acids. Instead, aCD patients showed increased levels of propionic, isohexanoic, and 2-ethylhexanoic acids, and a lower abundance of isovaleric and 2-methylbutyricacids when compared to HC. In addition, compared to aCD patients, pCD patients showed a higher abundance of isobutyric and octadecanoic acid. Finally, the immunological analysis of duodenal biopsy revealed a lower percentage of CD4
    Conclusion: The results of the present study show, for the first time, that the duodenal microbiota of patients with pCD does not differ substantially from that of aCD; however, serum FFAs and local T cells displayed a distinctive profile between pCD, aCD, and HC. In conclusion, our result may help to shed new light on the "gut microbiota-immunity axis," lipid metabolites, and duodenal immune response in overt CD and pCD patients, opening new paradigms in understanding the pathogenesis behind CD progression.
    Language English
    Publishing date 2022-09-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2022.886008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Combining liquid chromatography and tandem mass spectrometry approaches to the study of monoterpene glycosides (aroma precursors) in wine grape

    Flamini, Riccardo / Christine Mayr / Gianluca Bartolucci / Giovanna Danza / Marco Pallecchi / Marta Menicatti / Massimo Gardiman / Mirko De Rosso

    Journal of mass spectrometry. 2018 Sept., v. 53, no. 9

    2018  

    Abstract: Monoterpene‐glycosides are important aroma precursors that, undergo hydrolysis, confer intense floral notes to the wines. Therefore, the knowledge of the nature of the sugar residues and the structure of these molecules is of great interest. In present ... ...

    Abstract Monoterpene‐glycosides are important aroma precursors that, undergo hydrolysis, confer intense floral notes to the wines. Therefore, the knowledge of the nature of the sugar residues and the structure of these molecules is of great interest. In present study, liquid chromatography (LC) separation coupled with different mass spectrometry (MS) experiments for the characterization of these compounds were explored. The LC parameters were tuned to optimize the resolution between the analytes present in grape sample extracts. Twenty principal peaks with a relative abundance >1% were selected and divided in 4 classes characterized by different molecular weight. In general, positive ionization of the studied compounds displayed the [M + NH4]+ ion as base peak. On the contrary, a distribution between [M + Cl]− and [M + HCOO]− species was observed in negative ion mode. However, a clear differentiation between the studied compounds was only possible by combining both LC and tandem MS (MS/MS). Indeed, by applying a series of energy resolved MS/MS experiments and monitoring both positive and negative ions, a structural characterization of the analytes was achieved. The proposed LC‐MS/MS approach provided the profile of monoterpenol‐diglycosides and allowed the identification of a series of isobaric terpene‐diglycosides in grape. The study of their MS/MS spectra indicated the structure of geranic and/or nerolic acid aglycones. To verify the interest of studied compounds, a preliminary evaluation of the intensity of signals of these glycosides were carried out. The obtained results showed a significant difference between the grape samples collected in two different vintages.
    Keywords ammonium ; chemical species ; energy ; glycosides ; hydrolysis ; ionization ; liquid chromatography ; molecular weight ; monitoring ; monoterpenoids ; odors ; sugars ; tandem mass spectrometry ; wine grapes ; wines
    Language English
    Dates of publication 2018-09
    Size p. 792-800.
    Publishing place John Wiley & Sons, Ltd
    Document type Article
    Note JOURNAL ARTICLE
    ZDB-ID 1221763-3
    ISSN 1096-9888 ; 1076-5174
    ISSN (online) 1096-9888
    ISSN 1076-5174
    DOI 10.1002/jms.4212
    Database NAL-Catalogue (AGRICOLA)

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