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Naphthoquinone amino acid derivatives, synthesis and biological activity as proteasome inhibitors.

ABSTRACT: The ubiquitin-proteasome system has been largely investigated for its key role in protein degradation mechanisms that regulate both apoptosis and cell division. Because of their antitumour activity, different classes of proteasome inhibitors have been identified to date. Some of these compounds are currently employed in the clinical treatment of several types of cancer among which multiple myeloma. Here, we describe the design, chemistry, biological activity and modelling studies of a large series of amino acid derivatives linked to a naphthoquinone pharmacophoric group through variable spacers. Some analogues showed interesting inhibitory potency for the ?1 and ?5 subunits of the proteasome with IC50 values in the sub-µm range.

SUBMITTER: Marastoni M

PROVIDER: S-EPMC6445160 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Naphthoquinone amino acid derivatives, synthesis and biological activity as proteasome inhibitors.

Marastoni Mauro M Trapella Claudio C Scotti Alessandra A Fantinati Anna A Ferretti Valeria V Marzola Erika E Eleonora Gallerani G Gavioli Riccardo R Preti Delia D

Journal of enzyme inhibition and medicinal chemistry 20171201 1

The ubiquitin-proteasome system has been largely investigated for its key role in protein degradation mechanisms that regulate both apoptosis and cell division. Because of their antitumour activity, different classes of proteasome inhibitors have been identified to date. Some of these compounds are currently employed in the clinical treatment of several types of cancer among which multiple myeloma. Here, we describe the design, chemistry, biological activity and modelling studies of a large seri ...[more]

PMID: 28657369

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