Your browser doesn't support javascript.
loading
Novel Structural Insight into Inhibitors of Heme Oxygenase-1 (HO-1) by New Imidazole-Based Compounds: Biochemical and In Vitro Anticancer Activity Evaluation.
Greish, Khaled F; Salerno, Loredana; Al Zahrani, Reem; Amata, Emanuele; Modica, Maria N; Romeo, Giuseppe; Marrazzo, Agostino; Prezzavento, Orazio; Sorrenti, Valeria; Rescifina, Antonio; Floresta, Giuseppe; Intagliata, Sebastiano; Pittalà, Valeria.
Afiliación
  • Greish KF; Department of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama 329, Bahrain. khaledfg@agu.edu.bh.
  • Salerno L; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. l.salerno@unict.it.
  • Al Zahrani R; Department of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama 329, Bahrain. Alzahrani.reem11@gmail.com.
  • Amata E; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. eamata@unict.it.
  • Modica MN; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. mmodica@unict.it.
  • Romeo G; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. gromeo@unict.it.
  • Marrazzo A; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. marrazzo@unict.it.
  • Prezzavento O; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. prezzave@unict.it.
  • Sorrenti V; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. sorrenti@unict.it.
  • Rescifina A; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. arescifina@unict.it.
  • Floresta G; Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. giuseppe.floresta@unict.it.
  • Intagliata S; Department of Chemical Sciences, University of Catania, V.le A. Doria, 95125 Catania, Italy. giuseppe.floresta@unict.it.
  • Pittalà V; Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA. s.intagliata@cop.ufl.edu.
Molecules ; 23(5)2018 May 18.
Article en En | MEDLINE | ID: mdl-29783634
In this paper, the design, synthesis, and molecular modeling of a new azole-based HO-1 inhibitors was reported, using compound 1 as a lead compound, in which an imidazole moiety is linked to a hydrophobic group by means of an ethanolic spacer. The tested compounds showed a good inhibitor activity and possessed IC50 values in the micromolar range. These results were obtained by targeting the hydrophobic western region. Molecular modeling studies confirmed a consolidated binding mode in which the nitrogen of the imidazolyl moiety coordinated the heme ferrous iron, meanwhile the hydrophobic groups were located in the western region of HO-1 binding pocket. Moreover, the new compounds were screened for in silico ADME-Tox properties to predict drug-like behavior with convincing results. Finally, the in vitro antitumor activity profile of compound 1 was investigated in different cancer cell lines and nanomicellar formulation was synthesized with the aim of improving compound's 1 water solubility. Finally, compound 1 was tested in melanoma cells in combination with doxorubicin showing interesting synergic activity.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemo-Oxigenasa 1 / Imidazoles / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Bahrein Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hemo-Oxigenasa 1 / Imidazoles / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Bahrein Pais de publicación: Suiza