Design of First-in-Class Dual EZH2/HDAC Inhibitor: Biochemical Activity and Biological Evaluation in Cancer Cells.

Romanelli, Annalisa; Stazi, Giulia; Fioravanti, Rossella; Zwergel, Clemens; Di Bello, Elisabetta; Pomella, Silvia; Perrone, Clara; Battistelli, Cecilia; Strippoli, Raffaele; Tripodi, Marco; Del Bufalo, Donatella; Rota, Rossella; Trisciuoglio, Daniela; Mai, Antonello; Valente, Sergio

Romanelli, Annalisa; Stazi, Giulia; Fioravanti, Rossella; Zwergel, Clemens; Di Bello, Elisabetta; Pomella, Silvia; Perrone, Clara; Battistelli, Cecilia; Strippoli, Raffaele; Tripodi, Marco; Del Bufalo, Donatella; Rota, Rossella; Trisciuoglio, Daniela; Mai, Antonello; Valente, Sergio.

Afiliación

Romanelli A; Department of Drug Chemistry and Technologies, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Stazi G; Department of Drug Chemistry and Technologies, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Fioravanti R; Department of Drug Chemistry and Technologies, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Zwergel C; Department of Drug Chemistry and Technologies, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Di Bello E; Department of Medicine of Precision, University of Campania Luigi Vanvitelli, Via L. De Crecchio 7, 80138 Naples, Italy.
Pomella S; Department of Drug Chemistry and Technologies, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Perrone C; Department of Oncohematology, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy.
Battistelli C; Department of Oncohematology, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy.
Strippoli R; Department of Molecular Medicine, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Tripodi M; Department of Molecular Medicine, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Del Bufalo D; National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy.
Rota R; Department of Molecular Medicine, Sapienza University of Rome, P. le A. Moro 5, 00185 Rome, Italy.
Trisciuoglio D; National Institute for Infectious Diseases L. Spallanzani, IRCCS, Via Portuense 292, 00149 Rome, Italy.
Mai A; Preclinical Models and New Therapeutic Agents Unit, IRCCS Regina Elena National Cancer Institute, Viale Regina Elena 291,295, 00100 Rome, Italy.
Valente S; Department of Oncohematology, Bambino Gesù Children's Hospital, IRCCS, Viale San Paolo 15, 00146 Rome, Italy.

ACS Med Chem Lett ; 11(5): 977-983, 2020 May 14.

Article en En | MEDLINE | ID: mdl-32435414

ABSTRACT

ABSTRACT

Since the histone modifying enzymes EZH2 and HDACs control a number of epigenetic-dependent carcinogenic pathways, we designed the first-in-class dual EZH2/HDAC inhibitor 5 displaying (sub)micromolar inhibition against both targets. When tested in several cancer cell lines, the hybrid 5 impaired cell viability at low micromolar level and in leukemia U937 and rhabdomyosarcoma RH4 cells provided G1 arrest, apoptotic induction, and increased differentiation, associated with an increase of acetyl-H3 and acetyl-α-tubulin and a decrease of H3K27me3 levels. In glioblastoma U87 cells, 5 hampered epithelial to mesenchymal transition by increasing the E-cadherin expression, thus proposing itself as a useful candidate for anticancer therapy.

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: ACS Med Chem Lett Año: 2020 Tipo del documento: Article País de afiliación: Italia

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