In:
European Journal of Organic Chemistry, Wiley, Vol. 2018, No. 8 ( 2018-02-28), p. 1041-1052
Abstract:
Palmatine and berberine, structurally similar isoquinoline alkaloids exhibiting a broad range of biological activities, were recently found to inhibit p300 histone acetyltransferase (HAT), a potential therapeutic target for treating transcriptional activator‐driven malignancies and diseases. Here, we report the first total synthesis of B‐homo palmatine ( 11a ) and berberine ( 11b ) derivatives, which were synthesized from 3,4‐dimethoxybenzaldehyde ( 1a ) and benzo[ d ][1,3] dioxole‐5‐carbaldehyde ( 1b ) in nine steps in 13.8 and 16.9 % overall yields, respectively. A number of other new B‐homo palmatine and berberine derivatives were also prepared. These derivatives display good inhibitory activity against p300 HAT; compound 12a manifests the most potent inhibition with an IC 50 value of 0.42 µ m . Cell‐based assays revealed that 12a exhibits certain inhibitory activity against HCG27, HT1080, and Z‐138 cell lines, and no visible activity towards other cancer cell lines tested, reflecting that 12a has low cytotoxicity and acts against some types of cancer cells.
Type of Medium:
Online Resource
ISSN:
1434-193X
,
1099-0690
DOI:
10.1002/ejoc.v2018.8
DOI:
10.1002/ejoc.201701693
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
1475010-7