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Discovery of pyrrole derivatives for the treatment of glioblastoma and chronic myeloid leukemia.
Puxeddu, Michela; Shen, Hongliang; Bai, Ruoli; Coluccia, Antonio; Bufano, Marianna; Nalli, Marianna; Sebastiani, Jessica; Brancaccio, Diego; Da Pozzo, Eleonora; Tremolanti, Chiara; Martini, Claudia; Orlando, Viviana; Biagioni, Stefano; Sinicropi, Maria Stefania; Ceramella, Jessica; Iacopetta, Domenico; Coluccia, Addolorata Maria Luce; Hamel, Ernest; Liu, Te; Silvestri, Romano; La Regina, Giuseppe.
Afiliación
  • Puxeddu M; Laboratory Affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy.
  • Shen H; Department of Urology, Capital Medical University Beijing Friendship Hospital, Beijing, 100050, China.
  • Bai R; Molecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, United States.
  • Coluccia A; Laboratory Affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy.
  • Bufano M; Laboratory Affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy.
  • Nalli M; Laboratory Affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy.
  • Sebastiani J; Laboratory Affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy.
  • Brancaccio D; Department of Pharmacy, University of Naples"Federico II", Via Domenico Montesano 49, 80131, Naples, Italy.
  • Da Pozzo E; Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, I-56126, Pisa, Italy.
  • Tremolanti C; Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, I-56126, Pisa, Italy.
  • Martini C; Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, I-56126, Pisa, Italy.
  • Orlando V; Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy.
  • Biagioni S; Department of Biology and Biotechnologies "Charles Darwin", Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy.
  • Sinicropi MS; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, I-87036, Rende, Cosenza, Italy.
  • Ceramella J; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, I-87036, Rende, Cosenza, Italy.
  • Iacopetta D; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, I-87036, Rende, Cosenza, Italy.
  • Coluccia AML; Department of Biological and Environmental Sciences and Technologies, University of Salento, I-73100, Lecce, Italy.
  • Hamel E; Molecular Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, United States.
  • Liu T; Department of Biological and Environmental Sciences and Technologies, University of Salento, I-73100, Lecce, Italy; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 365 South Xiangyang Road, Shanghai, 200031, China. Electronic address: 0721160004
  • Silvestri R; Laboratory Affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy. Electronic address: romano.silvestri@uniroma1.it.
  • La Regina G; Laboratory Affiliated with the Institute Pasteur Italy - Cenci Bolognetti Foundation, Department of Drug Chemistry and Technologies, Sapienza University of Rome, Piazzale Aldo Moro 5, I-00185, Roma, Italy. Electronic address: giuseppe.laregina@uniroma1.it.
Eur J Med Chem ; 221: 113532, 2021 Oct 05.
Article en En | MEDLINE | ID: mdl-34052717
Long-term survivors of glioblastoma multiforme (GBM) are at high risk of developing second primary neoplasms, including leukemia. For these patients, the use of classic tyrosine kinase inhibitors (TKIs), such as imatinib mesylate, is strongly discouraged, since this treatment causes a tremendous increase of tumor and stem cell migration and invasion. We aimed to develop agents useful for the treatment of patients with GBM and chronic myeloid leukemia (CML) using an alternative mechanism of action from the TKIs, specifically based on the inhibition of tubulin polymerization. Compounds 7 and 25, as planned, not only inhibited tubulin polymerization, but also inhibited the proliferation of both GMB and CML cells, including those expressing the T315I mutation, at nanomolar concentrations. In in vivo experiments in BALB/cnu/nu mice injected subcutaneously with U87MG cells, in vivo, 7 significantly inhibited GBM cancer cell proliferation, in vivo tumorigenesis, and tumor growth, tumorigenesis and angiogenesis. Compound 7 was found to block human topoisomerase II (hTopoII) selectively and completely, at a concentration of 100 µM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mielógena Crónica BCR-ABL Positiva / Glioblastoma / Moduladores de Tubulina / Descubrimiento de Drogas / Compuestos Heterocíclicos / Metano / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Eur J Med Chem Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Francia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mielógena Crónica BCR-ABL Positiva / Glioblastoma / Moduladores de Tubulina / Descubrimiento de Drogas / Compuestos Heterocíclicos / Metano / Antineoplásicos Límite: Animals / Female / Humans Idioma: En Revista: Eur J Med Chem Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Francia