Heterocyclic bibenzimidazole derivatives as topoisomerase I inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 10, Issue 8, 2000, Pages 719-723

  Jin, Song ^a   Kim, Jung Sun ^a   Sim, Sai Peng ^b   Liu, Angela ^b   Pilch, Daniel S ^b,c   Liu, Leroy F ^b,c   Lavoie, Edmond J ^a,c  

^a RUTGERS UNIVERSITY   (United States)

^b UNIVERSITY OF MEDICINE AND DENTISTRY OF NEW JERSEY   (United States)

^c RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZIMIDAZOLE DERIVATIVE; DNA TOPOISOMERASE; DNA TOPOISOMERASE INHIBITOR;

ARTICLE; CYTOTOXICITY; DNA BINDING; ENZYME INHIBITION; HUMAN; HYDROGEN BOND; LYMPHOBLAST; STRUCTURE ACTIVITY RELATION; TOXICITY TESTING; TUMOR CELL LINE;

BENZIMIDAZOLES; DNA TOPOISOMERASES, TYPE I; ENZYME INHIBITORS; HETEROCYCLIC COMPOUNDS; SPECTRUM ANALYSIS;

EID: 0034678478     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(00)00087-1     Document Type: Article

References (14)

1. Chen A.Y., Yu C., Bodley A.L., Peng L.F., Liu L.F. Cancer Res. 53:1993;1332.
2. Chen A., Yu C., Gatto B., Liu L.F. Proc. Natl. Acad. Sci. USA. 90:1993;8131.
3. Beerman T.A., McHugh M.M., Sigmund R., Lown J.W., Rao K.E., Bathni Y. Biochem. Biophys. Acta. 1131:1992;53.
4. Sun Q., Gatto B., Yu C., Liu A., Liu L.F., LaVoie E.J. J. Med. Chem. 38:1995;3638.
5. Xu Z., Li T.-K., Kim J.S., LaVoie E.J., Breslauer K.J., Liu L.F., Pilch D.S. Biochemistry. 37:1998;3558.
6. Pilch D.S., Xu Z., Sun Q., LaVoie E.J., Liu L.F., Breslauer K.J. Proc. Natl. Acad. Sci. USA. 94:1997;13565.
7. Kim J.S., Yu C., Liu A., Liu L.F., LaVoie E.J. J. Med. Chem. 40:1997;2818.
8. Rangarajan, M.; Kim, J. S.; Song Jin, S.; Sim, S-P; Liu, A.; Pilch, D. S.; Liu, L. F.; LaVoie, E. J. Bioorg. Med. Chem. in press.
9. A mixture of 2[2′-(1″-methylbenzimidazol-5″-yl)benzimidazol-5′-yl] benzimidazole and 2[2′-(1″-methylbenzimidazol-6″-yl)benzimidazol-5′-yl] benzimidazole were prepared by the coupling of intermediate 7 with a mixture of 1-methyl-5-formyl- and 1-methyl-6-formylbenzimidazole. Bioassays were performed with the resulting mixture of products.
10. Rewcastle G.W., Palmer B.D., Bridges A.J., Hollis-Showalter H.D., Sun L., Nelson J., McMichael A., Kraker A.J., Fry D.W., Denny W.A. J. Med. Chem. 39:1996;918.
11. Jones R.G., McLaughlin K.C. Org. Synth. 30:1950;86.
12. Ohmori J., Kubota H., Shimizu-Sasamata M., Okada M., Sakamoto S. J. Med. Chem. 39:1996;1331.
13. Moyer M.P., Shiurba J.F., Rapoport H. J. Org. Chem. 51:1986;5106.
14. Molecular modeling was performed with PC Spartan Pro, Wavefunction, Inc. (Irvine, CA). Four of the lower energy conformers associated with rotation about the 2′-bond between the bibenzenzimidazole and the attached heterocycle were selected and interatomic bond lengths between the atoms specified in Table 2 were determined.