Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 51, Issue 24, Pages 7820-7826Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm800993r
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- NCI NIH HHS [CA-127892-01A, R01 CA127892-01A1, R01 CA127892] Funding Source: Medline
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Synthesis and identification of novel phenylalkyl isoselenocyanates (ISCs), isosteric selenium analogues of naturally occurring phenylalkyl isothiocyanates (ITCs), as effective cytotoxic and antiturnor 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. IC50 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.
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