2. Academic Validation
  3. Targeting heme Oxygenase-1 with hybrid compounds to overcome Imatinib resistance in chronic myeloid leukemia cell lines

Targeting heme Oxygenase-1 with hybrid compounds to overcome Imatinib resistance in chronic myeloid leukemia cell lines

  • Eur J Med Chem. 2018 Oct 5:158:937-950. doi: 10.1016/j.ejmech.2018.09.048.
Valeria Sorrenti 1,  Valeria Pittalà 2,  Giuseppe Romeo 1,  Emanuele Amata 1,  Maria Dichiara 1,  Agostino Marrazzo 1,  Rita Turnaturi 1,  Orazio Prezzavento 1,  Ignazio Barbagallo 1,  Luca Vanella 1,  Antonio Rescifina 1,  Giuseppe Floresta 3,  Daniele Tibullo 4,  Francesco Di Raimondo 5,  Sebastiano Intagliata 6,  Loredana Salerno 7
Affiliations

Affiliations

  • 1 Department of Drug Sciences, University of Catania, viale A. Doria 6, 95125, Catania, Italy.
  • 2 Department of Drug Sciences, University of Catania, viale A. Doria 6, 95125, Catania, Italy. Electronic address: vpittala@unict.it.
  • 3 Department of Drug Sciences, University of Catania, viale A. Doria 6, 95125, Catania, Italy; Department of Chemical Sciences, University of Catania, viale A. Doria 6, 95125, Catania, Italy.
  • 4 Division of Hematology, A.O.U. Policlinico-OVE, University of Catania, via S. Sofia, 78, 95123, Catania, Italy; Department of Biomedical and Biotechnological Sciences, University of Catania, via S. Sofia, 78, 95123, Catania, Italy.
  • 5 Division of Hematology, A.O.U. Policlinico-OVE, University of Catania, via S. Sofia, 78, 95123, Catania, Italy.
  • 6 Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA.
  • 7 Department of Drug Sciences, University of Catania, viale A. Doria 6, 95125, Catania, Italy. Electronic address: l.salerno@unict.it.
PMID: 30261468 DOI: 10.1016/j.ejmech.2018.09.048
Abstract

Heme oxygenase-1 (HO-1) is a cytoprotective Enzyme and a survival-enhancing factor in a number of cancers. Chronic myeloid leukemia (CML) is a blood Cancer caused by pathological kinase activity of the Bcr-Abl protein, currently treated with tyrosine kinase inhibitors (TKIs) such as Imatinib (IM). However, resistance to TKIs persists in a number of patients and HO-1 overexpression has been linked with the induction of chemoresistance in CML. With this in mind, in this study, we designed and synthesized the first series of hybrid compounds obtained by combining the structures of IM, as Bcr-Abl Inhibitor, with imidazole-based HO-1 inhibitors. We found that many hybrids were able to inhibit the enzymatic activity of both targets and to reduce the viability of CML-IM resistant cells, showing that a single molecular entity may reduce the resistance phenomenon.

Keywords

BCR-ABL; Chronic myeloid leukemia; HO-1 inhibitors; Imatinib; Tyrosine kinase inhibitors.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z