Synthesis and biological assays of E-ring analogs of camptothecin and homocamptothecin

• Published in: Bioorganic & medicinal chemistry Vol. 14; no. 18; pp. 6202 - 6212
• Main Authors: Tangirala, Raghuram S., Antony, Smitha, Agama, Keli, Pommier, Yves, Anderson, Bradley D., Bevins, Robert, Curran, Dennis P.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-09-2006; Elsevier Science
• Subjects: Anti-cancer agents; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biological Assay; Camptothecin; Camptothecin - analogs & derivatives; Camptothecin - chemical synthesis; Camptothecin - chemistry; Camptothecin - pharmacology; Cascade radical annulation; Cell Line, Tumor; Cell Proliferation - drug effects; DNA - drug effects; Drug Screening Assays, Antitumor; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; General aspects; Humans; Magnetic Resonance Spectroscopy; Medical sciences; Models, Molecular; Molecular Structure; Pharmacology. Drug treatments; Structure-Activity Relationship; Topoisomerase 1; Topoisomerase Inhibitors; Camptothecin; Topoisomerase 1; Cascade radical annulation; Anti-cancer agents; Antineoplastic agent; Organic hydrazide; Ether; Enzyme; DNA topoisomerase; Lactam; Amides; Lactone; In vitro; Biological activity; Annelation; Alkaloid; Isomerases; Hydroxyacid; Cleavage; Chemical synthesis
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2006.05.073

Analogs of the anti-tumor agent camptothecin with both closed E-rings (lactone and ether) and open E-rings (reduced acid, hydrazide, and protected Weinreb amide) have been prepared and tested in topoisomerase and cellular assays. The results provide insights into the structural features of the camptothecin E-ring that affect biological activity.
Analogs of the anti-tumor agent camptothecin with both closed E-rings (lactone and ether) and open E-rings (reduced acid, hydrazide, and protected Weinreb amide) have been prepared and tested in topoisomerase and cellular assays. The results provide insights into the structural features of the camptothecin E-ring that affect biological activity.