Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Feb 16;8(4):589-92.
doi: 10.1021/ol052800q.

Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues

Paul A Wender  1 , Orion D Jankowski, Kate Longcore, Elie A Tabet, Haruo Seto, Taijiro Tomikawa
Affiliations

Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues

Paul A Wender et al. Org Lett. .

Abstract

[structure: see text] Apoptolidin (1) exhibits potent and highly selective apoptosis inducing activity against sensitive cancer cell lines and is hypothesized to act by inhibition of mitochondrial F(0)F(1)-ATP synthase. A series of apoptolidin derivatives, including a new intermolecular Diels-Alder adduct, were analyzed for antiproliferative activity in E1A-transformed rat fibroblasts. Potent F(0)F(1)-ATPase inhibition was not a sufficient determinant of antiproliferative activity for several analogues, suggesting the existence of a secondary biological target or more complex mode of action for apoptolidin.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structures of apoptolidin and hydroxyl derivatives.
Figure 2
Figure 2
Structure of isoapoptolidin.
Figure 3
Figure 3
Structures of apoptolidin fragmentation products.
Scheme 1
Scheme 1
Diels-Alder adduct of apoptolidin.
Figure 4
Figure 4
Three-dimensional structure of the macrocyclic core of adduct 15. Methyl protons, tert-butyl group, and C-9 and C-20 substituents are omitted for clarity.
Figure 5
Figure 5
Structure of oligomycin A.
None
See this image and copyright information in PMC

References

    1. Kim JW, Adachi H, Shin-ya K, Hayakawa Y, Seto H. J. Antibiotics. 1997;50:628. - PubMed
    2. Hayakawa Y, Kim JW, Adachi H, Shin-ya K, Fujita K, Seto H. J. Am. Chem Soc. 1998;120:3524.
    1. Salomon AR, Voehringer DW, Herzenberg LA, Khosla C. Proc. Natl. Acad. Sci. U.S.A. 2000;97:14766. - PMC - PubMed
    2. Salomon AR, Voehringer DW, Herzenberg LA, Khosla C. Chem. Biol. 2001;8:71. - PubMed
    3. Salomon AR, Zhang Y, Seto H, Khosla C. Org. Lett. 2001;3:57. - PubMed
    1. Wehlan H, Dauber M, Fernaud MTM, Schuppan J, Mahrwald R, Ziemer B, Garcia MEJ, Koert U. Angew. Chem. Int. Ed. 2004;43:2597. - PubMed
    2. Nicolaou KC, Fylaktakidou KC, Monenschein H, Li YW, Weyershausen B, Mitchell HJ, Wei HX, Guntupalli P, Hepworth D, Sugita K. J. Am. Chem. Soc. 2003;125:15433. - PubMed
    3. Nicolaou KC, Li YW, Sugita K, Monenschein H, Guntupalli P, Mitchell HJ, Fylaktakidou KC, Vourloumis D, Giannakakou P, O'Brate A. J. Am. Chem. Soc. 2003;125:15443. - PubMed
    1. Bouchez LC, Vogel P. Chem. Eur. J. 2005;11:4609. - PubMed
    2. Crimmins MT, Christie HS, Chaudhary K, Long A. J. Am. Chem. Soc. 2005;127:13810. - PubMed
    3. Jin B, Liu Q, Sulikowski GA. Tetrahedron. 2005;61:401.
    4. Wu B, Liu QS, Sulikowski GA. Angew. Chem. Int. Ed. 2004:6673–6675. - PubMed
    5. Abe K, Kato K, Arai T, Rahim MA, Sultana I, Matsumura S, Toshima K. Tetrahedron Lett. 2004;45:8849.
    6. Paquette WD, Taylor RE. Org. Lett. 2004;6:103. - PubMed
    7. Chng SS, Xu J, Loh TP. Tetrahedron Lett. 2003;44:4997.
    8. Chen Y, Evarts JB, Torres E, Fuchs PL. Org. Lett. 2002;4:3571. - PubMed
    1. Wender PA, Jankowski OD, Tabet EA, Seto H. Org. Lett. 2003;5:487. - PubMed

Publication types

MeSH terms