title: Synthesis and anticancer activity comparison of phenylalkyl isoselenocyanates with corresponding naturally occurring and synthetic isothiocyanates.
abstract: Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antitumor agents are described. The structure-activity relationship comparison of ISCs with ITCs and effect of the increasing alkyl chain length in inhibiting cancer cell growth were evaluated on melanoma, prostate, breast, glioblastoma, sarcoma, and colon cancer cell lines. IC(50) values for ISC compounds were generally lower than their corresponding ITC analogues. Similarly, in UACC 903 human melanoma cells, the inhibition of cell proliferation and induction of apoptosis were more pronounced with ISCs compared to ITCs. Further, ISCs and ITCs effectively inhibited melanoma tumor growth in mice following intraperitoneal xenograft. A similar reduction in tumor size was observed at 3 times lower doses of ISCs compared to corresponding ITCs.
authors.affiliation: Department of Pharmacology, Penn State Hershey College of Medicine, Hershey, Pennsylvania 17033, USA. aks14@psu.edu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Arati
authors.initials: A
authors.lastname: Sharma
authors.forename: Dhimant
authors.initials: D
authors.lastname: Desai
authors.forename: SubbaRao V
authors.initials: SV
authors.lastname: Madhunapantula
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Huh
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Robertson
authors.forename: Shantu
authors.initials: S
authors.lastname: Amin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D017879:Isothiocyanates / Q000737:chemistry*; D051379:Mice; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D017879:Isothiocyanates