Phenylpyrrole-based HDAC inhibitors: synthesis, molecular modeling and biological studies-Reference-Cited by-同舟云学术

Phenylpyrrole-based HDAC inhibitors: synthesis, molecular modeling and biological studies

Published:2016-09 Issue:13 Volume:8 Page:1573-1587
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Brindisi Margherita¹,Cavella Caterina¹,Brogi Simone¹,Nebbioso Angela²³,Senger Johanna⁴,Maramai Samuele¹,Ciotta Alfonso²³,Iside Concetta²³,Butini Stefania¹,Lamponi Stefania¹,Novellino Ettore⁵,Altucci Lucia²³,Jung Manfred⁴,Campiani Giuseppe¹,Gemma Sandra¹

Affiliation:

1. European Research Centre for Drug Discovery & Development (NatSynDrugs), University of Siena, via Aldo Moro 2, 53100 Siena, Italy

2. Department of Biochemistry, Biophysics & General Pathology, Second University of Napoli, Vico Luigi De Crecchio 7, 80138 Napoli, Italy

3. Institute of Genetics and Biophysics Adriano Buzzati-Traverso, IGB-CNR, Via Pietro Castellino 111, 80131 Napoli, Italy

4. Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstraße 25, 79104 Freiburg, Germany

5. Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy

Abstract

Aim: Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in the initiation and progression of cancer. Currently, three hydroxamate-containing HDAC pan-inhibitors have been approved as antitumor agents. Results: We herein present the development of a series of novel phenylpyrrole-based derivatives stemmed from combined computational and medicinal chemistry efforts to rationally modulate HDAC1/6 isoform selectivity. In vitro activity on HDAC1 and HDAC6 isoforms and the effects of selected analogs on histone H3 and α-tubulin acetylation levels were determined. Cell-based data evidenced, for selected compounds, a promising antitumor potential and low toxicity on normal cells. Conclusion: The newly developed compounds represent a valuable starting point for the development of novel anticancer agents.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

http://www.future-science.com/doi/pdf/10.4155/fmc-2016-0068

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