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

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 rig...