Synthesis and anticancer activity of sclerophytin-inspired hydroisobenzofurans.
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 IC(50)'s of 1-3 microM in growth inhibitory assays against KB3 cells. The NCI 60-cell line 5-dose assay for analog 6h revealed a GI(50)=0.148 microM and LC(50)=9.36 microM for the RPMI-8226 leukemia cell line, and a GI(50)=0.552 microM and LC(50)=26.8 microM for the HOP-92 non-small cell lung cancer cell line.
Bateman
T David
TD
Department of Chemistry and Biochemistry, 119 Chemistry Building, University of Arkansas, Fayetteville, AR 72701, USA.
Joshi
Aarti L
AL
Moon
Kwangyul
K
Galitovskaya
Elena N
EN
Upreti
Meenakshi
M
Chambers
Timothy C
TC
McIntosh
Matthias C
MC
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D005663:Furans; C412667:sclerophytin A