Site-specific chiral ruthenium (II) and cobalt (III) antitumor a

Details Site-specific chiral ruthenium (II) and cobalt (III) antitumor a Site-specific chiral ruthenium (II) and cobalt (III) antitumor a

1985-01-18

1987-10-13

Kepplinger, Esther M.

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

935 78, 20415772, 546 88, 435 6, 424131, C12Q 168, C07H 2100, A61K 3324, C07D47104

Patent

active

046999787

ABSTRACT:
This invention concerns a coordination complex of the formula (R).sub.2 --M--(Y).sub.2 wherein M comprises a suitable transition metal, e.g. cobalt or ruthenium, R comprises 1,10-phenanthroline or a substituted derivative thereof, Y comprises a labile ligand, e.g. chloride, tartrate, malonate or ascorbate ion and R and Y are bonded to M by coordination bonds.
A complex of this invention may be used for covalently labeling DNA with a complex of the formula (R).sub.2 --M, wherein R and M are as previously defined. A complex of this invention which contains cobalt may also be used in a method for nicking DNA by effecting single-stranded scission of at least one phosphodiester bond of the DNA with ultraviolet radiation.
A complex of this invention is further useful in a method for killing tumor cells. A pharmaceutical composition for the treatment of tumor cells in a subject may be prepared containing an effective anti-tumor amount of a complex of this invention and a pharmaceutically acceptable carrier. Such a composition may be used for treating a subject afflicted with tumor cells so as to cause regression of the tumor cells.

REFERENCES:
patent: 4547569 (1985-10-01), Letsinger et al.
Pope, L. M., et al, J. Biol. Chem., vol. 257, Oct. 1982, pp. 12121-12128.
Barton, J. K., et al, J. Am. Chem. Soc., vol. 106, No. 7, 1984, pp. 2172-2176.
Chang, C. H., et al, Biochemistry, vol. 21, 1982, pp. 6332-6334.
Barton, J. K., et al, J. Am. Chem. Soc., vol. 104, No. 18, 1982, pp. 4967-4969.
Chang, C. H., et al, Biochemistry, vol. 23, 1984, pp. 2268-2274.
Pommier, Y. et al, Biochemistry, vol. 23, No. 14, 1984, pp. 3194-3201.
Letsinger, R. L. et al, J. Am. Chem. Soc., vol. 103, 1981, pp. 7394-7396.

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