Antineoplastic Agents. 585. Isolation of Bridelia ferruginea Anticancer Podophyllotoxins and Synthesis of 4-Aza-podophyllotoxin Structural Modifications1
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- 作者：George R. Pettit ; Justin D. Searcy ; Rui Tan ; Gordon M. Cragg ; Noeleen Melody ; John C. Knight ; Jean-Charles Chapuis
- 刊名：Journal of Natural Products
- 出版年：2016
- 出版时间：March 25, 2016
- 年：2016
- 卷：79
- 期：3
- 页码：507-518
- 全文大小：551K
- ISSN：1520-6025
文摘
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.