La Regina, Giuseppe, Bai, Ruoli, Coluccia, Antonio, Famiglini, Valeria, Passacantilli, Sara, Naccarato, Valentina, Ortar, Giorgio, Mazzoccoli, Carmela, Ruggieri, Vitalba, Agriesti, Francesca, Piccoli, Claudia, Tataranni, Tiziana, Nalli, Marianna, Brancale, Andrea  ORCID: https://orcid.org/0000-0002-9728-3419, Vultaggio, Stefania, Mercurio, Ciro, Varasi, Mario, Saponaro, Concetta, Sergio, Sara, Maffia, Michele, Coluccia, Addolorata Maria Luce, Hamel, Ernest and Silvestri, Romano
2017.
3-Aroyl-1,4-diarylpyrroles inhibit chronic myeloid leukemia cell growth through an interaction with tubulin.
ACS Medicinal Chemistry Letters
8
(5)
, pp. 521-526.
10.1021/acsmedchemlett.7b00022
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Abstract
We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4-phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM)-sensitive KBM5-WT or its IM-resistant KBM5-T315I mutation. Compound 10 minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML.
| Item Type: | Article |
|---|---|
| Date Type: | Published Online |
| Status: | Published |
| Schools: | Schools > Pharmacy |
| Subjects: | R Medicine > RS Pharmacy and materia medica |
| Uncontrolled Keywords: | Cancer, tubulin, chronic myeloid leukemia, synthesis, 3-aroyl-1,4-diarylpyrrole |
| Publisher: | American Chemical Society |
| ISSN: | 1948-5875 |
| Date of First Compliant Deposit: | 7 June 2017 |
| Date of Acceptance: | 26 April 2017 |
| Last Modified: | 12 Nov 2024 15:00 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/101273 |
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