Design of chalcogen-containing norepinephrines: efficient GPx mimics and strong cytotoxic agents against HeLa cells

Marset A, Begines P, López Ó, Maya I, García-Aranda N, Schwartz S Jr, Abasolo I, Fernández-Bolaños JG.

Future Med Chem. 2016 Dec;8(18):2185-2195. Epub 2016 Nov 15.

https://www.ncbi.nlm.nih.gov/pubmed/27845568

Abstract

AIM:

Numerous chronic diseases exhibit multifactorial etiologies, so focusing on a single therapeutic target is usually an inadequate treatment; instead, multi-target drugs are preferred. Herein, a panel of phenolic thioureas and selenoureas were designed as new prototypes against multifactorial diseases concerning antioxidation and cytotoxicity, as a pro-oxidant environment is usually found in such diseases.

RESULTS:

Selenoureas were excellent antiradical agents and biomimetic catalysts of glutathione peroxidase for the scavenging of H2O2. They were also potent and selective cytotoxic agents against cancer cells, in particular HeLa (IC50 2.77-6.13 μM), apoptosis being involved. Selenoureas also reduced oxidative stress in HeLa cells (IC50= 3.76 μM).

CONCLUSION:

Phenolic selenoureas are promising lead structures for the development of drugs targeting multifactorial diseases like cancer.

KEYWORDS:

GPx mimics; antioxidants; catechol; cytotoxic agents; selenoureas