Novel Methylselenoesters as Antiproliferative Agents
AbstractSelenium (Se) compounds are potential therapeutic agents in cancer. Importantly, the biological effects of Se compounds are exerted by their metabolites, with methylselenol (CH3SeH) being one of the key executors. In this study, we developed a new series of methylselenoesters with different scaffolds aiming to modulate the release of CH3SeH. The fifteen compounds follow Lipinski’s Rule of Five and with exception of compounds 1 and 14, present better drug-likeness values than the positive control methylseleninic acid. The compounds were evaluated to determine their radical scavenging activity. Compound 11 reduced both DPPH and ABTS radicals. The cytotoxicity of the compounds was evaluated in a panel of five cancer cell lines (prostate, colon and lung carcinoma, mammary adenocarcinoma and chronic myelogenous leukemia) and two non-malignant (lung and mammary epithelial) cell lines. Ten compounds had GI50 values below 10 μM at 72 h in four cancer cell lines. Compounds 5 and 15 were chosen for further characterization of their mechanism of action in the mammary adenocarcinoma cell line due to their similarity with methylseleninic acid. Both compounds induced G2/M arrest whereas cell death was partially executed by caspases. The reduction and metabolism were also investigated, and both compounds were shown to be substrates for redox active enzyme thioredoxin reductase. View Full-Text
- Supplementary File 1:
Supplementary (PDF, 7731 KB)
Share & Cite This Article
Díaz-Argelich, N.; Encío, I.; Plano, D.; Fernandes, A.P.; Palop, J.A.; Sanmartín, C. Novel Methylselenoesters as Antiproliferative Agents. Molecules 2017, 22, 1288.
Díaz-Argelich N, Encío I, Plano D, Fernandes AP, Palop JA, Sanmartín C. Novel Methylselenoesters as Antiproliferative Agents. Molecules. 2017; 22(8):1288.Chicago/Turabian Style
Díaz-Argelich, Nuria; Encío, Ignacio; Plano, Daniel; Fernandes, Aristi P.; Palop, Juan Antonio; Sanmartín, Carmen. 2017. "Novel Methylselenoesters as Antiproliferative Agents." Molecules 22, no. 8: 1288.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.