Intensely potent doxorubicin analogues: Structure-activity relationship

Journal of Medicinal Chemistry

Volumn 41, Issue 6, 1998, Pages 965-972

  Farquhar, David ^a   Cherif, Abdallah ^a   Bakina, Elena ^a   Arly Nelson, J ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOXORUBICIN DERIVATIVE; ESTERASE; GLYCOPROTEIN P; N (5,5 DIACETOXYPENT 1 YL)DOXORUBICIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CELL GROWTH; CYTOTOXICITY; DRUG HYDROLYSIS; DRUG POTENCY; DRUG STRUCTURE; GROWTH INHIBITION; MOUSE; NONHUMAN;

ANIMALS; ANTINEOPLASTIC AGENTS; CARBOXYLESTERASE; CARBOXYLIC ESTER HYDROLASES; CELL DIVISION; CHO CELLS; CRICETINAE; DOXORUBICIN; DRUG RESISTANCE; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; P-GLYCOPROTEIN; TUMOR CELLS, CULTURED;

EID: 0032510381     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9706980     Document Type: Article

References (19)

1. Farquhar, D.; Newman, R. A.; Zuckerman, J.; Andersson, B. S. Doxorubicin analogues incorporating chemically reactive substituents. J. Med. Chem. 1991, 34, 561-564.
2. Cherif, A.; Farquhar, D. N-(5,5-Diacetoxypent-l-yl)doxorubicin: A new intensely potent doxorubicin analogue. J. Med. Chem. 1992, 35, 3208-3214.
3. Bakina, E.; Wu, Z.; Rosenblum, M.; Farquhar, D. Intensely cytotoxic anthracycline prodrugs. J. Med. Chem. 1997, 40, 40134018.
4. Krisch, K. In Carboxylic Ester Hydrolases, The Enzymes, Vol. 5; Boyer, P. D., Ed.; Academic Press: New York, 1971; pp 43-69.
5. Wang, Y.; Farquhar, D. Aldophosphamide acetal diacetate and structural analogues: Synthesis and cytotoxicity studies. J. Med. Chem. 1991, 34, 197-203.
6. Zwelling, L. A.; Altshuler, E.; Cherif, A.; Farquhar, D. N-(5,5Diacetoxypent-1-yDdoxorubicin hydrochloride. A novel anthracycline producing interstrand cross-linking and rapid endonucleolytic cleavage in human leukemia cells containing either intercalator sensitive or intercalator resistant topoisomerase II. Cancer Res. 1991, 51, 6704-6707.
7. Griffith, W. P.; Ley, S. V.; Whitcombe, G. P.; White, A. D. Preparation and use of tetra-n-butylammonium perruthenate (TBAP reagent) and tetra-n- propylammonium perruthenate (TPAP reagent) as new catalytic oxidants for alcohols. J. Chem. Soc., Chem. Commun. 1987, 1625-1627.
8. The purpose of these studies was to determine whether the compounds would be easily hydrolyzed in the presence of an excess of the putative activating enzyme. No effort was made to study the hydrolysis kinetics of each compound as this would require limiting amounts of the esterase.
9. Sen, S.; Teeter, L. D.; Kuo, T. Specific gene amplification associated with consistent chromosomal abnormality in independently established multidrug resistant Chinese hamster ovary cells. Chromosoma 1987, 95, 117-125.
10. Acton, E. M.; Tong, G. L.; Mosher, C. W.; Wolgemuth, R. L. Intensely potent morpholinyl anthracyclines. J. Med. Chem. 1984, 27, 638-645.
11. Farquhar, D.; Wu, Z. Covalent modification of DNA by the sugar moiety of doxorubicin. Proc. Am. Assoc. Cancer Res. 1994, 35, 364.
12. Frederick, C. A.; Williams, L. D.; Ughetto, G.; van der Marel, G. A.; van Boom, J. H.; Rich, A. Structural comparison of anticancer drug-DNA complexes: Adriamycin and daunomycin. Biochemistry 1990, 29, 2538-2549.
13. Wang, A. H.; Gao, Y. G.; Liaw, Y. C.; Lin, Y. K. Formaldehyde cross-links daunomycin and DNA efficiently: HPLC and X-ray diffraction studies. Biochemistry 1991, 30, 3812-3815.
14. Whittaker, M.; McArthur, C. R.; Leznoff, C. C. Asymmetric synthesis towards (3Z,6R)-3-methyl-6-isopropenyl-3,9-decadien1-yl acetate, a component of the Californian red scale pheromone. Can. J. Chem. 1985, 63, 2844-2852.
15. Bohlmann, F.; Niedballa, U.; Schneider, J. Polyacetylene compounds. Synthesis of naturally occurring Cn polyynes. Chem. Ber. 1965, 98, 3010-3014.
16. Lebel, N. A.; Post, M. E.; Whang, J. J. The addition of nitrones to olefins. Fused bicyclic isoxazolidincs. J. Am, Chem. Soc. 1964, 86, 3759-3767.
17. This compound was a generous gift from Alfrebro Inc., 1055 Reed Rd, Monroe, OH 45050.
18. Wilson, S. R.; Zucker, P. A.; Kirn, C. W.; Villa, C. A. A new reaction of organosilicon chemistry. The oxidative fragmentation of y-hydroxysilanes. Tetrahedron Lett. 1985,26, 1969-1972.
19. Dishong, D. M.; Diamond, C. J.; Cinoman, M. L; Gokel, G. W. Crown cation complex effects. 20. Syntheses and cation binding properties of carbon-pivot lariat ethers. J. Am. Chem. Soc. 1983, 105, 586-593.