Design and synthesis of a potent phorboxazole C(11-15) acetal analogue.
[structure: see text] We disclose here the design, synthesis, and biological evaluation of simplified Z- and E-C(2-3) alkynyl phorboxazole C(11-15) acetals (+)-7Z and (+)-7E, wherein the Z-isomer proved to be a potent nanomolar cytotoxic agent. Reevaluation of (+)-C(45-46) E-chloroalkenyl phorboxazole A (6) confirms subnanomolar activity across a broad panel of human cancer cell lines.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Razler
Thomas M
TM
Meis
Regina M
RM
Pettit
George R
GR
D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408887:phorboxazole A