2. Academic Validation
  3. Chalcones and Chalcone-mimetic Derivatives as Notch Inhibitors in a Model of T-cell Acute Lymphoblastic Leukemia

Chalcones and Chalcone-mimetic Derivatives as Notch Inhibitors in a Model of T-cell Acute Lymphoblastic Leukemia

  • ACS Med Chem Lett. 2019 Feb 26;10(4):639-643. doi: 10.1021/acsmedchemlett.8b00608.
Deborah Quaglio 1,  Nadezda Zhdanovskaya 2,  Gloria Tobajas 3,  Viviana Cuartas 3,  Silvia Balducci 1,  Michael S Christodoulou 4,  Giancarlo Fabrizi 1,  Marta Gargantilla 3,  Eva-María Priego 3,  Álvaro Carmona Pestaña 2,  Daniele Passarella 5,  Isabella Screpanti 2,  Bruno Botta 1,  Rocco Palermo 2,  Mattia Mori 6,  Francesca Ghirga 7,  María-Jesús Pérez-Pérez 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Technology of Drugs, "Department of Excellence 2018-2022", Sapienza Università di Roma, P.le Aldo Moro 5, 00185 Rome, Italy.
  • 2 Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy.
  • 3 Instituto de Química Médica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
  • 4 DISFARM, Sezione di Chimica Generale e Organica "A. Marchesini", Università degli Studi di Milano, Via Venezian 21, 20133 Milano, Italy.
  • 5 Dipartimento di Chimica, Università degli Studi di Milano, Via Golgi, 19, 20133 Milano, Italy.
  • 6 Department of Biotechnology, Chemistry and Pharmacy, "Department of Excellence 2018-2022", University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
  • 7 Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena 291, 00161 Rome, Italy.
PMID: 30996810 DOI: 10.1021/acsmedchemlett.8b00608
Abstract

Based on hit-likeness and chemical diversity, a number of Chalcones and chalcone-mimetic compounds were selected as putative Notch inhibitors. The evaluation of the antiproliferative effect combined with the inhibition of Notch1 expression in KOPTK1 cell line identified compound 18, featuring a tetrahydronaphthalene-based scaffold, as a new promising Notch-blocking agent.

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