title: Novel seleno- and thio-urea derivatives with potent in vitro activities against several cancer cell lines.
abstract: A series of novel selenourea derivatives and corresponding thiourea analogs were synthesized and tested against a panel of six human cancer cell lines: melanoma (1205Lu), lung carcinoma (A549), prostatic carcinoma (DU145), colorectal carcinoma (HCT116), pancreatic epithelioid carcinoma (PANC-1) and pancreatic adenocarcinoma (BxPC3). In general, we found that the selenium-containing derivatives were more potent than their isosteric sulfur analogs. Four selenourea derivatives (1e, 1f, 1g and 1i) showed IC50 values below 10 μM in all of tested cell lines at 72 h. On the basis of its potent activity, compound 1g was selected for further biological evaluation in different colon cancer cell lines. Our results indicated that compound 1g induced apoptosis by caspase activation, along with inhibition of anti-apoptotic proteins.
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA; Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008 Pamplona, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Alcolea
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA; Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008 Pamplona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Plano
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Deepkamal N
authors.initials: DN
authors.lastname: Karelia
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008 Pamplona, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Palop
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
authors.forename: Shantu
authors.initials: S
authors.lastname: Amin
authors.affiliation: Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008 Pamplona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Sanmartín
authors.affiliation: Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA. Electronic address: aks14@psu.edu.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; C081959:selenourea; D014508:Urea; D013890:Thiourea
keywords: Apoptosis; Cytotoxicity; Selenium; Selenourea