Laccase-Catalyzed 1,4-Dioxane-Mediated Synthesis of Belladine N-Oxides with Anti-Influenza A Virus Activity

Zippilli, Claudio; Botta, Lorenzo; Bizzarri, Bruno Mattia; Nencioni, Lucia; Angelis, Marta De; Protto, Virginia; Giorgi, Gianluca; Baratto, Maria Camilla; Pogni, Rebecca; Saladino, Raffaele

doi:10.3390/ijms22031337

Cited by 10 publications

(8 citation statements)

References 55 publications

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“…The ICW assay was performed using the Odyssey Imaging System (LI-COR, Lincoln, NE, USA) as previously described. 41,42 Briey, A549 cells grown in 96-well plates (2 Â 10 4 cells per well) infected with PR8, and treated or not with high concentrations (100, 150 and 200 mg mL À1 ) of selected compounds were xed with 4% formaldehyde, washed, permeabilized with 0.1% Triton X-100 and incubated with Odyssey Blocking Buffer for 1 h (LI-COR Biosciences, Lincoln, NE, USA). The cells were then stained at 4 C overnight with mouse anti HA (Santa Cruz Biotechnology, Germany) diluted in Odyssey Blocking Buffer.…”

Section: In Cell Western (Icw) Assaymentioning

confidence: 99%

Aminomalononitrile inspired prebiotic chemistry as a novel multicomponent tool for the synthesis of imidazole and purine derivatives with anti-influenza A virus activity

et al. 2021

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Section: In Cell Western (Icw) Assaymentioning

confidence: 99%

Aminomalononitrile inspired prebiotic chemistry as a novel multicomponent tool for the synthesis of imidazole and purine derivatives with anti-influenza A virus activity

et al. 2021

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“…Therefore, rats were injected with nonradioactive CS1P1, and plasma was collected at appropriate times to extract Our observation is consistent with literature reports that N-tertiary amines are readily metabolized in vivo into mono-oxidates. 23,31 Together, our data suggested that the molecular structure of major lipophilic radiometabolite observed in human plasma sample is the N-oxide [ 11 C] TZ82121 (Scheme 3).…”

Section: Discussionmentioning

confidence: 68%

Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer

Qiu,

Jiang,

Cho

et al. 2024

ACS Chem. Neurosci.

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The sphingosine-1-phosphate receptor 1 (S1PR1) radiotracer [ 11 C]CS1P1 has shown promise in proof-of-concept PET imaging of neuroinflammation in multiple sclerosis (MS). Our HPLC radiometabolite analysis of human plasma samples collected during PET scans with [ 11 C]CS1P1 detected a radiometabolite peak that is more lipophilic than [ 11 C]CS1P1. Radiolabeled metabolites that cross the blood-brain barrier complicate quantitative modeling of neuroimaging tracers; thus, characterizing such radiometabolites is important. Here, we report our detailed investigation of the metabolite profile of [ 11 C]CS1P1 in rats, nonhuman primates, and humans. CS1P1 is a fluorine-containing ligand that we labeled with C-11 or F-18 for preclinical studies; the brain uptake was similar for both radiotracers. The same lipophilic radiometabolite found in human studies also was observed in plasma samples of rats and NHPs for CS1P1 labeled with either C-11 or F-18. We characterized the metabolite in detail using rats after injection of the nonradioactive CS1P1. To authenticate the molecular structure of this radiometabolite, we injected rats with 8 mg/kg of CS1P1 to collect plasma for solvent extraction and HPLC injection, followed by LC/MS analysis of the same metabolite. The LC/MS data indicated in vivo mono-oxidation of CS1P1 produces the metabolite. Subsequently, we synthesized three different mono-oxidized derivatives of CS1P1 for further investigation. Comparing the retention times of the mono-oxidized derivatives with the metabolite observed in rats injected with CS1P1 identified the metabolite as N-oxide 1, also named TZ82121. The MS fragmentation pattern of N-oxide 1 also matched that of the major metabolite in rat plasma. To confirm that metabolite TZ82121 does not enter the brain, we radiosynthesized [ 18 F]TZ82121 by the oxidation of [ 18 F]FS1P1. Radio-HPLC analysis confirmed that [ 18 F]TZ82121 matched the radiometabolite observed in rat plasma post injection of [ 18 F] FS1P1. Furthermore, the acute biodistribution study in SD rats and PET brain imaging in a nonhuman primate showed that [ 18 F] TZ82121 does not enter the rat or nonhuman primate brain. Consequently, we concluded that the major lipophilic radiometabolite N-oxide [ 11 C]TZ82121, detected in human plasma post injection of [ 11 C]CS1P1, does not enter the brain to confound quantitative PET data analysis. [ 11 C]CS1P1 is a promising S1PR1 radiotracer for detecting S1PR1 expression in the CNS.

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“…This and other reactions concerning the MC synthesis of antiviral agents have been recently reported [67]. Due to the increase of in drug-resistance phenomena, as well as novel Influenza virus mutations, novel mechanisms for the inhibition of human influenza virus have been explored [10][11][12][13].…”

Section: Synthesis Of Oseltamivirmentioning

confidence: 98%

“…Recently Quadrelli et al dedicated a chapter of a book to the cycloaddition reactions used for the synthesis of antiviral compounds [7], and a recent review described the biocatalytic routes applied to antiviral agents [8]. Taking into consideration our experience in the antiviral field [9][10][11][12][13][14][15][16][17][18] and in the application of DAR to the synthesis of antiviral agents [15,18] we were interested to investigate this topic in more detail. We show some examples in which the catalytic DARs furnish useful optically active intermediates for the synthesis of selected bioactive compounds after a brief introduction of enantioselective DAR.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Enantioselective Diels Alder Reaction: Application in the Synthesis of Antiviral Agents

Grillo

Bizzarri

2022

Catalysts

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The Diels–Alder reaction (DAR) is one of the most effective and reliable strategies for the construction of six-membered carbocyclic and heterocyclic rings, and it is widely used in the synthesis of organic molecules and drugs. Due to the high regio- and stereo-selectivity and its versatility, DARs have represented a powerful tool for organic chemistry for many years. In addition, the asymmetric DAR has become a fundamental synthetic approach in the preparation of optically active six-membered rings and natural compounds. The COVID-19-related pandemic requires continuous research; DAR represents an useful method to obtain optically active intermediates for the synthesis of antiviral agents under different catalytic conditions. We would like to highlight an intriguing synthetic procedure applied to the development of novel synthetic protocols that are potentially useful against a large panel of viruses and other unmet diseases.

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Laccase-Catalyzed 1,4-Dioxane-Mediated Synthesis of Belladine N-Oxides with Anti-Influenza A Virus Activity

Cited by 10 publications

References 55 publications

Aminomalononitrile inspired prebiotic chemistry as a novel multicomponent tool for the synthesis of imidazole and purine derivatives with anti-influenza A virus activity

Aminomalononitrile inspired prebiotic chemistry as a novel multicomponent tool for the synthesis of imidazole and purine derivatives with anti-influenza A virus activity

Metabolite Study and Structural Authentication for the First-in-Human Use Sphingosine-1-phosphate Receptor 1 Radiotracer

Catalytic Enantioselective Diels Alder Reaction: Application in the Synthesis of Antiviral Agents

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