Stereocontrolled synthesis of new iminosugar lipophilic derivatives and evaluation of biological activities

Martina De Angelis; Ludovica Primitivo; Carla Sappino; Barbara Centrella; Claudia Lucarini; Lucrezia Lanciotti; Alessia Petti; Davide Odore; Andrea D'Annibale; Beatrice Macchi; Valeria Stefanizzi; Angela Cirigliano; Teresa Rinaldi; Giuliana Righi; Alessandra Ricelli

doi:10.1016/j.carres.2023.108984

Stereocontrolled synthesis of new iminosugar lipophilic derivatives and evaluation of biological activities

Carbohydr Res. 2023 Dec:534:108984. doi: 10.1016/j.carres.2023.108984. Epub 2023 Nov 15.

Authors

Affiliations

¹ Department of Chemistry, "Sapienza" University of Rome, P.le A. Moro 5, 00185, Rome, Italy. Electronic address: m.deangelis@uniroma1.it.
² Department of Chemistry, "Sapienza" University of Rome, P.le A. Moro 5, 00185, Rome, Italy.
³ Department of Chemical Science and Technology, University of Rome "Tor Vergata", Via Cracovia, 50, 00133, Rome, Italy.
⁴ Institute of Molecular Biology and Pathology (IBPM)-CNR, P.le A. Moro 5, 00185, Rome, Italy.
⁵ Department of Biology and Biotechnology, "Sapienza" University of Rome, P.le A. Moro 5, 00185, Rome, Italy.

PMID: 37984279
DOI: 10.1016/j.carres.2023.108984

Abstract

Iminosugars' similarity to carbohydrates determines the exceptional potential for this class of polyhydroxylated alkaloids to serve as potential drug candidates for a wide variety of diseases such as diabetes, lysosomal storage diseases, cancer, bacterial and viral infections. The presence of lipophilic substituents has a significant impact on their biological activities. This work reports the synthesis of three new pyrrolidine lipophilic derivatives O-alkylated in C-6 position. The biological activities of our iminosugars' collection were tested in two cancer cell lines and, due to the pharmaceutical potential, in the model yeast system Saccharomyces cerevisiae to assess their toxicity.

Keywords: Iminosugar derivatives; Lipophilic iminosugars; Saccharomyces cerevisiae; Stereocontrolled synthesis; U937 and CAL-27 metabolic inhibitors.

MeSH terms

Enzyme Inhibitors
Imino Sugars* / pharmacology

Substances

Imino Sugars
Enzyme Inhibitors