Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 11, Issue 5, Pages 889-894Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.9b00661
Keywords
Sigma receptors; nitric oxide; nitric oxide donors; cancer; bifunctional ligands
Categories
Funding
- Universita degli Studi di Catania, Piano per la Ricerca 2016-2018 [57722172105, 57722172114]
Ask authors/readers for more resources
We report the development of molecular hybrids in which a nitrate group serving as nitric oxide (NO) donor is covalently joined to sigma receptor ligands to give candidates for double-targeted cancer therapy. The compounds have been evaluated in radioligand binding assay at both sigma receptors and selected compounds tested for NO release. Compounds 9, 15, 18, 19, and 21 were subjected to MTT test. Compound 15 produced a significant reduction of MCF-7 and Caco-2 cellular viability with comparable IC50 as doxorubicin, being also not toxic for fibroblast HFF-1 cells. Compound 15 has shown a sigma(1), receptor antagonist/sigma(2) receptor agonist profile. Two derivatives of compound 15 lacking the nitrate group did not induce a reduction of MCF-7 cellular viability, suggesting a potential synergistic effect between the sigma receptors and the NO-mediated events. Overall, the combination of NO donor and sigma receptors ligands provided compounds with beneficial effects for the treatment of cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available