Abstract
Cytotoxic constituents of the terrestrial plant Bridelia ferruginea were isolated using bioactivity-guided fractionation, which revealed the presence of the previously known deoxypodophyllotoxin (1), isopicrodeoxypodophyllotoxin (2), β-peltatin (3), β-peltatin-5-O-β-d-glucopyranoside (3a), and the indole neoechinulin (4). As an extension of previous podophyllotoxin research, SAR studies were undertaken focused on 4-aza-podophyllotoxin structural modifications. A number of such derivatives were synthesized following modifications to the A and E rings. Such structural modifications with alkyl and 4-fluorobenzyl substituents at the 4-aza position provided the most potent cancer cell growth inhibitory activity (GI50 0.1 to <0.03 μg/mL) against a panel of six human cancer cell lines and one murine cancer cell line. Several compounds corresponding to 4′-demethylated modifications were also synthesized and found to be significantly less potent.
Original language | English (US) |
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Pages (from-to) | 507-518 |
Number of pages | 12 |
Journal | Journal of Natural Products |
Volume | 79 |
Issue number | 3 |
DOIs | |
State | Published - Mar 25 2016 |
ASJC Scopus subject areas
- Analytical Chemistry
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry