In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates

Beatriz Romano; Daniel Plano; Ignacio Encío; Juan Antonio Palop; Carmen Sanmartín

doi:10.1016/j.bmc.2015.02.048

In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates

Bioorg Med Chem. 2015 Apr 15;23(8):1716-27. doi: 10.1016/j.bmc.2015.02.048. Epub 2015 Mar 4.

Authors

Beatriz Romano¹, Daniel Plano¹, Ignacio Encío², Juan Antonio Palop³, Carmen Sanmartín¹

Affiliations

¹ Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain.
² Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain; Departamento de Ciencias de la Salud, Universidad Pública de Navarra, Avda. Barañain s/n, E-31008 Pamplona, Spain.
³ Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain; Instituto de Investigaciones Sanitarias de Navarra (IDISNA), Irunlarrea, 3, E-31008 Pamplona, Spain. Electronic address: jpalop@unav.es.

PMID: 25792142
DOI: 10.1016/j.bmc.2015.02.048

Abstract

Novel selenocyanate and diselenide derivatives containing a carbamate moiety were synthesised and evaluated in vitro to determine their cytotoxic and radical scavenging properties. Cytotoxic activity was tested against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds displayed high antiproliferative activity with GI50 values below 10μM in MCF-7, CCRF-CEM and PC-3 cells. Radical scavenging properties of the new selenocompounds were confirmed testing their ability to scavenge DPPH and ABTS radicals. Based on the activity of selenium-based glutathione peroxidases (GPxs), compounds 1a, 2e and 2h were further screened for their capacity to reduce hydrogen peroxide under thiol presence. Results suggest that compound 1a mimics GPxs activity. Cytotoxic parameters, radical scavenging activity and ADME profile point to 1a as promising drug candidate.

Keywords: ABTS(+); Carbamate; Cytotoxicity; DPPH; GPx; Radical scavenging; Selenium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects*
Cyanates / chemistry
Cyanates / pharmacology*
Free Radical Scavengers / chemistry
Free Radical Scavengers / pharmacology*
Humans
Neoplasms / drug therapy*
Organoselenium Compounds / chemistry
Organoselenium Compounds / pharmacology*
Selenium Compounds / chemistry
Selenium Compounds / pharmacology*

Substances

Antineoplastic Agents
Cyanates
Free Radical Scavengers
Organoselenium Compounds
Selenium Compounds
selenocyanic acid