1,3,4-Oxadiazole-containing histone deacetylase inhibitors: anticancer activities in cancer cells.

Abstract

We describe 1,3,4-oxadiazole-containing hydroxamates (2) and 2-aminoanilides (3) as histone deacetylase inhibitors. Among them, 2t, 2x, and 3i were the most potent and selective against HDAC1. In U937 leukemia cells, 2t was more potent than SAHA in inducing apoptosis, and 3i displayed cell differentiation with a potency similar to MS-275. In several acute myeloid leukemia (AML) cell lines, as well as in U937 cells in combination with doxorubicin, 3i showed higher antiproliferative effects than SAHA.

• Authors: Sergio Valente, Daniela Trisciuoglio, Teresa De Luca, Angela Nebbioso, Donatella Labella, Alessia Lenoci, Chiara Bigogno, Giulio Dondio, Marco Miceli, Gerald Brosch, Donatella Del Bufalo, Lucia Altucci, Antonello Mai
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 57 Issue 14 Pg. 6259-65 (Jul 24 2014) ISSN: 1520-4804 [Electronic] United States
• PMID: 24972008 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Histone Deacetylase Inhibitors
• Oxadiazoles
• 1,3,4-oxadiazole
• Doxorubicin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Doxorubicin (pharmacology)
• Drug Screening Assays, Antitumor
• HCT116 Cells
• HL-60 Cells
• Histone Deacetylase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Humans
• Molecular Structure
• Oxadiazoles (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured