Target directed enediyne prodrugs: Cytotoxic estrogen conjugates

Tetrahedron Letters

Volumn 37, Issue 21, 1996, Pages 3643-3646

  Jones, Graham B ^a   Huber, Robert S ^a   Mathews, Jude E ^a   Li, Aiwen ^a  

^a GREENVILLE HOSPITAL SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CONJUGATED ESTROGEN; CYTOTOXIC AGENT; MITOMYCIN C; PRODRUG;

ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CONTROLLED STUDY; DNA CLEAVAGE; DRUG SYNTHESIS; HUMAN; HUMAN CELL;

MINK CELL FOCUS-FORMING VIRUS;

EID: 0029930813     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00662-4     Document Type: Article

References (16)

1. 'Cytotoxic Estrogens in Hormone Receptive Tumors' Raus, J. ; Leclercq, G. ; Martens, H. ; eds. Academic Press, London, 1980.
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4. Katzenellenbogen, J. A. ; In 'Proceeding of the Robert A. Welch Foundation - Chemistry at the Frontiers of Medicine' 1991, 35, P. 229-257.
5. For reviews see: Nicolaou, K. C. ; Smith, A. L. ; Yue, E. W. ; Proc. Natl. Acad. Sci. USA 1993, 90, 5881; Nicolaou, K.C.; Dai, W.M.; Angew. Chem. Intl. Ed. Engl. 1991, 30, 1387.
6. For reviews see: Nicolaou, K. C. ; Smith, A. L. ; Yue, E. W. ; Proc. Natl. Acad. Sci. USA 1993, 90, 5881; Nicolaou, K.C.; Dai, W.M.; Angew. Chem. Intl. Ed. Engl. 1991, 30, 1387.
7. Jones, G. B. ; Huber, R. S. ; Tetrahedron Lett. 1994, 35, 2655.
8. Jones, G. B. ; Huber, R. S.; US Patent 5,436,361.
9. Jones, G. B. ; Huber, R. S. ; Mathews, J. E. ; J. Chem. Soc. Chem. Commun. 1995, 1791.
10. Cells were maintained in phenol red-free medium containing charcoal stripped serum to mitigate any endogenous estrogen effects. Full details of bioassay protocols for this and other related enediynes will be published elsewhere. For details of the thymidine assay see: McConnuaghie, A. W. ; Jenkins, T. C. ; J. Med. Chem. 1995, 38, 3488.
11. All incubations were performed with ΦX174 Type I DNA (New England Biolabs, 50 μM in base pairs) at pH 8.5 in tris-HCl buffer. Electrophoresis was conducted on a 1% agarose gel and stained with ethidium bromide. Conversion to type II form was evident at agent (12) concentration of 50 μM, and pronounced at 500 μM, with traces of type III form evident.
12. Nique, F. ; Van de Velde, P. ; Bremaud, J. ; Hardy, M. ; Philbert, D. ; Teutsch, G. ; J. Steroid Biochem. Molec. Biol. 1994, 50, 21; Wakeling, A. E. ; Bowler, J. ; J. Steroid Biochem. 1988, 30, 141; Bowler, J. ; Lilley, T. J. ; Pittam, J. D. ; Wakeling, A. E. ; Steroids 1989, 54, 71; Claussner, A. ; Nedelec, L. ; Nique, F. ; Philibert, D. ; Teutsch, G. ; Van de Velde, P. ; J. Steroid Biochem. Molec. Biol. 1992, 41, 609.
13. Nique, F. ; Van de Velde, P. ; Bremaud, J. ; Hardy, M. ; Philbert, D. ; Teutsch, G. ; J. Steroid Biochem. Molec. Biol. 1994, 50, 21; Wakeling, A. E. ; Bowler, J. ; J. Steroid Biochem. 1988, 30, 141; Bowler, J. ; Lilley, T. J. ; Pittam, J. D. ; Wakeling, A. E. ; Steroids 1989, 54, 71; Claussner, A. ; Nedelec, L. ; Nique, F. ; Philibert, D. ; Teutsch, G. ; Van de Velde, P. ; J. Steroid Biochem. Molec. Biol. 1992, 41, 609.
14. Nique, F. ; Van de Velde, P. ; Bremaud, J. ; Hardy, M. ; Philbert, D. ; Teutsch, G. ; J. Steroid Biochem. Molec. Biol. 1994, 50, 21; Wakeling, A. E. ; Bowler, J. ; J. Steroid Biochem. 1988, 30, 141; Bowler, J. ; Lilley, T. J. ; Pittam, J. D. ; Wakeling, A. E. ; Steroids 1989, 54, 71; Claussner, A. ; Nedelec, L. ; Nique, F. ; Philibert, D. ; Teutsch, G. ; Van de Velde, P. ; J. Steroid Biochem. Molec. Biol. 1992, 41, 609.
15. Nique, F. ; Van de Velde, P. ; Bremaud, J. ; Hardy, M. ; Philbert, D. ; Teutsch, G. ; J. Steroid Biochem. Molec. Biol. 1994, 50, 21; Wakeling, A. E. ; Bowler, J. ; J. Steroid Biochem. 1988, 30, 141; Bowler, J. ; Lilley, T. J. ; Pittam, J. D. ; Wakeling, A. E. ; Steroids 1989, 54, 71; Claussner, A. ; Nedelec, L. ; Nique, F. ; Philibert, D. ; Teutsch, G. ; Van de Velde, P. ; J. Steroid Biochem. Molec. Biol. 1992, 41, 609.
16. For a recent example of a potentially useful enediyne-steroid hybrid see: Wang, J. ; DeClercq, P. J. ; Angew. Chem. Intl. Ed. 1995, 34, 1749.