Chemoenzymatic synthesis and antileukemic activity of novel C9- and C14-functionalized parthenolide analogs

摘要: Abstract Parthenolide is a naturally occurring terpene with promising anticancer properties, particularly in the context of acute myeloid leukemia (AML). Optimization this natural product has been challenged by limited opportunities for late-stage functionalization molecule without affecting pharmacologically important α-methylene-γ-lactone moiety. Here, we report further development and application chemoenzymatic strategy to afford series new analogs parthenolide functionalized at aliphatic positions C9 C14. Several these compounds were determined be able kill cells patient-derived primary AML specimens improved activity compared parthenolide, exhibiting LC 50 values low micromolar range. These studies demonstrate that different O–H chemistries can applied elaborate scaffold modifications or C14 position effectively enhance antileukemic properties product. The C9-functionalized 22a 25b identified as most interesting terms potency selectivity toward versus healthy blood cells.