Synthesis and anticancer activity of sclerophytin-inspired hydroisobenzofurans

by Bateman, Terry David; Joshi, Aarti L.; Moon, Kwangyul; Galitovskaya, Elena N.; Upreti, Meenakshi; Chambers, Timothy C.; McIntosh, Matt C.

Three structurally related sets of hydroisobenzofuran analogs of sclerophytin A were prepared in three or four steps from (S)-(+)-carvone via an aldol-cycloaldol sequence. The most potent members of each set of analogs exhibited IC50's of 1-3 mu M in growth inhibitory assays against KB3 cells. The NCI 60-cell line 5-dose assay for analog 6h revealed a GI(50) = 0.148 mu M and LC50 = 9.36 mu M for the RPMI-8226 leukemia cell line, and a GI(50) = 0.552 mu M and LC50 = 26.8 mu M for the HOP-92 non-small cell lung cancer cell line. (C) 2009 Elsevier Ltd. All rights reserved.

Journal
Bioorganic and Medicinal Chemistry Letters
Volume
19
Issue
24
Year
2009
Start Page
6898
ISBN/ISSN
1464-3405; 0960-894X
PMID
19896844
DOI
10.1016/j.bmcl.2009.10.079