Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives.
A series of A-ring and E-ring analogues of the natural product luotonin A, a known topoisomerase I poison, was evaluated for growth inhibition in human carcinoma and leukemia cell lines. Rational design of structures was based on analogues of the related alkaloid camptothecin, which has been demonstrated to exert cytotoxic effects by the same mechanism of action. When compared to luotonin A, several compounds exhibited an improved topoisomerase I-dependent growth inhibition of a human leukemia cell line.
Nacro
Kassoum
K
Discovery Research & Development, Albany Molecular Research Inc., Albany, NY 12213-5098, USA.
Zha
Conxiang Charles
CC
Guzzo
Peter R
PR
Jason Herr
R
R
Peace
Denise
D
Friedrich
Thomas D
TD
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011758:Pyrroles; D011809:Quinones; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C480761:luotonin A