These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


PUBMED FOR HANDHELDS

Search MEDLINE/PubMed


  • Title: Discovery of novel 17-phenylethylaminegeldanamycin derivatives as potent Hsp90 inhibitors.
    Author: Li Z, Jia L, Wang J, Wu X, Shi G, Lu C, Shen Y.
    Journal: Chem Biol Drug Des; 2015 Feb; 85(2):181-8. PubMed ID: 24903735.
    Abstract:
    Twenty-six 17-phenylethylamine-modified geldanamycin derivatives were synthesized and evaluated for antiproliferation activity in human cancer cell lines, LNCaP and MDA-MB-231. Five derivatives (2j, 2q, 2v, 2x, and 2 y) showed excellent in vitro antitumor activities. Among them, compound 2 y was the most potent lead, with IC50 values of 0.27 ± 0.11 and 0.86 ± 0.23 μm for LNCaP and MDA-MB-231, respectively. In particular, compound 2 y was more active than its precursor geldanamycin against LNCap cells. Liver injury test in mice demonstrated that 2 y group showed no significant difference for serum alanine aminotransferase (ALT) activity versus vehicle control, indicating that 2 y was a promising antitumor candidate. Preliminary structure-activity relationship (SAR) and molecular dynamics (MD) simulations of this new series of geldanamycin derivatives were also investigated, suggesting a theoretical model of 17-phenylethylaminegeldanamycins binding to Hsp90.
    [Abstract] [Full Text] [Related] [New Search]