Abstract
The hedgehog (Hh) signaling pathway plays crucial roles in cell maintenance and proliferation during embryonic development. Naturally occurring Hh inhibitors were isolated from Artocarpus communis and Hyptis suaveolens using our previously constructed cell-based assay system. Bioactivity guided fractionation led to the isolation of 15 compounds, including seven new compounds (4, 5, 6, 7, and 9-11). The isolated compounds showed cytotoxicity against a cancer cell line (PANC1) in which Hh signaling was abnormally activated. Several compounds (12-14; GLI1 transcriptional inhibition IC50 = 7.6, 4.7, and 4.0 μM, respectively) inhibited Hh related protein (BCL2) expression. Moreover, compounds 1, 12, and 13 disrupted GLI1 and DNA complex formation.
Original language | English |
---|---|
Pages (from-to) | 4150-4154 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 23 |
Issue number | 15 |
DOIs | |
Publication status | Published - 2015 Jul 23 |
Externally published | Yes |
Keywords
- Artocarpus communis
- Hedgehog signal
- Hyptis suaveolens
- Inhibitor
- Natural products
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry