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
  • 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.