New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells

In this paper, a novel series of imidazole-based heme oxygenase-1 (HO-1) inhibitors is reported. These compounds were obtained by modifications of previously described high potent and selective arylethanolimidazoles. In particular, simplification of the central linker and repositioning of the hydrop...

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Main Authors:	Valeria Ciaffaglione, Sebastiano Intagliata, Valeria Pittalà, Agostino Marrazzo, Valeria Sorrenti, Luca Vanella, Antonio Rescifina, Giuseppe Floresta, Ameera Sultan, Khaled Greish, Loredana Salerno
Format:	Article
Language:	English
Published:	MDPI AG 2020-03-01
Series:	International Journal of Molecular Sciences
Subjects:	heme oxygenase ho-1 imidazole inhibitors structure–activity relationships anticancer
Online Access:	https://www.mdpi.com/1422-0067/21/6/1923

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spelling	doaj-8f4a9369c575475888ac65dd384a8b742020-11-25T01:41:51ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-03-01216192310.3390/ijms21061923ijms21061923New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer CellsValeria Ciaffaglione0Sebastiano Intagliata1Valeria Pittalà2Agostino Marrazzo3Valeria Sorrenti4Luca Vanella5Antonio Rescifina6Giuseppe Floresta7Ameera Sultan8Khaled Greish9Loredana Salerno10Department of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama 329, BahrainDepartment of Molecular Medicine, College of Medicine and Medical Sciences, Princess Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama 329, BahrainDepartment of Drug Sciences, University of Catania, viale A. Doria 6, 95125 Catania, ItalyIn this paper, a novel series of imidazole-based heme oxygenase-1 (HO-1) inhibitors is reported. These compounds were obtained by modifications of previously described high potent and selective arylethanolimidazoles. In particular, simplification of the central linker and repositioning of the hydrophobic portion were carried out. Results indicate that a hydroxyl group in the central region is crucial for the potency as well as the spatial distribution of the hydrophobic portion. Docking studies revealed a similar interaction of the classical HO-1 inhibitors with the active site of the protein. The most potent and selective compound (<b>5a</b>) was tested for its potential cytotoxic activity against hormone-sensitive and hormone-resistant breast cancer cell lines (MCF-7 and MDA-MB-231).https://www.mdpi.com/1422-0067/21/6/1923heme oxygenaseho-1imidazoleinhibitorsstructure–activity relationshipsanticancer
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Valeria Ciaffaglione Sebastiano Intagliata Valeria Pittalà Agostino Marrazzo Valeria Sorrenti Luca Vanella Antonio Rescifina Giuseppe Floresta Ameera Sultan Khaled Greish Loredana Salerno
spellingShingle	Valeria Ciaffaglione Sebastiano Intagliata Valeria Pittalà Agostino Marrazzo Valeria Sorrenti Luca Vanella Antonio Rescifina Giuseppe Floresta Ameera Sultan Khaled Greish Loredana Salerno New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells International Journal of Molecular Sciences heme oxygenase ho-1 imidazole inhibitors structure–activity relationships anticancer
author_facet	Valeria Ciaffaglione Sebastiano Intagliata Valeria Pittalà Agostino Marrazzo Valeria Sorrenti Luca Vanella Antonio Rescifina Giuseppe Floresta Ameera Sultan Khaled Greish Loredana Salerno
author_sort	Valeria Ciaffaglione
title	New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells
title_short	New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells
title_full	New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells
title_fullStr	New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells
title_full_unstemmed	New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells
title_sort	new arylethanolimidazole derivatives as ho-1 inhibitors with cytotoxicity against mcf-7 breast cancer cells
publisher	MDPI AG
series	International Journal of Molecular Sciences
issn	1422-0067
publishDate	2020-03-01
description	In this paper, a novel series of imidazole-based heme oxygenase-1 (HO-1) inhibitors is reported. These compounds were obtained by modifications of previously described high potent and selective arylethanolimidazoles. In particular, simplification of the central linker and repositioning of the hydrophobic portion were carried out. Results indicate that a hydroxyl group in the central region is crucial for the potency as well as the spatial distribution of the hydrophobic portion. Docking studies revealed a similar interaction of the classical HO-1 inhibitors with the active site of the protein. The most potent and selective compound (<b>5a</b>) was tested for its potential cytotoxic activity against hormone-sensitive and hormone-resistant breast cancer cell lines (MCF-7 and MDA-MB-231).
topic	heme oxygenase ho-1 imidazole inhibitors structure–activity relationships anticancer
url	https://www.mdpi.com/1422-0067/21/6/1923
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New Arylethanolimidazole Derivatives as HO-1 Inhibitors with Cytotoxicity against MCF-7 Breast Cancer Cells

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