Rigid Analogs of Camptothecin as DNA Topoisomerase I Inhibitors

• Published in: Journal of medicinal chemistry Vol. 38; no. 6; pp. 906 - 911
• Main Authors: Lackey, Karen, Besterman, Jeffrey M, Fletcher, Wade, Leitner, Peter, Morton, Bradley, Sternbach, Daniel D
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.03.1995; Amer Chemical Soc
• Subjects: Alkaloids - chemical synthesis; Alkaloids - pharmacology; Analytical, structural and metabolic biochemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Camptothecin - analogs & derivatives; Chemistry, Medicinal; DNA - metabolism; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Isomerases; Isomerism; Life Sciences & Biomedicine; Models, Molecular; Molecular Structure; Pharmacology & Pharmacy; Science & Technology; Structure-Activity Relationship; Topoisomerase I Inhibitors; PLANT ANTITUMOR AGENTS; 20(S)-CAMPTOTHECIN; CLEAVAGE; RING; Isomerases; Structure activity relation; Enzyme; DNA topoisomerase; Lactam; Enzyme inhibitor; Steric hindrance; Lactone; Chemical synthesis; In vitro; Oxygen nitrogen heterocycle
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00006a008

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.