Synthesis and biological assays of E-ring analogs of camptothecin and homocamptothecin.
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.
Tangirala
Raghuram S
RS
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Antony
Smitha
S
Agama
Keli
K
Pommier
Yves
Y
Anderson
Bradley D
BD
Bevins
Robert
R
Curran
Dennis P
DP
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001681:Biological Assay; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059003:Topoisomerase Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059003:Topoisomerase Inhibitors; D004247:DNA; C120029:homocamptothecin; D002166:Camptothecin