Sigma Receptor Ligands Carrying a Nitric Oxide Donor Nitrate Moiety: Synthesis, In Silico, and Biological Evaluation

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2020 May 22

PMID 32435401

Citations 8

Authors

Emanuele Amata

Maria Dichiara

Davide Gentile

Agostino Marrazzo

Rita Turnaturi

Emanuela Arena

Alfonsina La Mantia

Barbara Rita Tomasello

Rosaria Acquaviva

Claudia Di Giacomo

Antonio Rescifina

Orazio Prezzavento

Affiliations

Soon will be listed here.

Abstract

We report the development of molecular hybrids in which a nitrate group serving as nitric oxide (NO) donor is covalently joined to σ receptor ligands to give candidates for double-targeted cancer therapy. The compounds have been evaluated in radioligand binding assay at both σ receptors and selected compounds tested for NO release. Compounds , , , , and were subjected to MTT test. Compound produced a significant reduction of MCF-7 and Caco-2 cellular viability with comparable IC as doxorubicin, being also not toxic for fibroblast HFF-1 cells. Compound has shown a σ receptor antagonist/σ receptor agonist profile. Two derivatives of compound lacking the nitrate group did not induce a reduction of MCF-7 cellular viability, suggesting a potential synergistic effect between the σ receptors and the NO-mediated events. Overall, the combination of NO donor and σ receptors ligands provided compounds with beneficial effects for the treatment of cancer.

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