Rigid analogs of camptothecin as DNA topoisomerase I inhibitors

K Lackey; J M Besterman; W Fletcher; P Leitner; B Morton; D D Sternbach

doi:10.1021/jm00006a008

Rigid analogs of camptothecin as DNA topoisomerase I inhibitors

J Med Chem. 1995 Mar 17;38(6):906-11. doi: 10.1021/jm00006a008.

Authors

K Lackey¹, J M Besterman, W Fletcher, P Leitner, B Morton, D D Sternbach

Affiliation

¹ Glaxo Research Institute, Research Triangle Park, North Carolina 27709.

PMID: 7699706
DOI: 10.1021/jm00006a008

Abstract

Substituted 8-ethyl-2-(2-oxo-1,2-dihydroindol-3-ylidene)-8-hydroxy-2,3,5,8- tetrahydro-6-oxa-3a-azacyclopenta[b]naphthalene-1,4,7-triones were synthesized and evaluated as topoisomerase I inhibitors in an in vitro cleavable complex assay. The activity of these compounds may be attributed to their rigid, planar geometry, and an attempt was made to correlate the SAR in this series to known attributes of camptothecin.

Publication types

Comparative Study

MeSH terms

Alkaloids / chemical synthesis*
Alkaloids / pharmacology*
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology*
Camptothecin / analogs & derivatives*
DNA / metabolism
Isomerism
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Topoisomerase I Inhibitors*

Substances

Alkaloids
Antineoplastic Agents
Topoisomerase I Inhibitors
DNA
Camptothecin