New bioactive constituents from the leaves of Annona glabra
Abstract
The objective of this project has been to find new bioactive anticancer principles from the leaves of Annona glabra L. (Annonaceae), a tropical tree distributed mainly in the Americas and in Southeast Asia. The phytochemistry of the Annonaceae suggested that the acetogenins were likely to be the most important anticancer agents behind its folklore. Indeed, the brine shrimp lethality test (BST), in activity-directed investigation of the leaves, revealed a total of nineteen structurally diverse bioactive Annonaceous; acetogenins as well as two non-acetogenin bioactive compounds. Of all the twenty-one bioactive compounds isolated, eleven (1–4, 7, 8, and 16–20) were new to the literature. The structure of these new compounds were determined through careful spectral analyses including UV, IR, CIMS, EIMS, ID-NMR and 2D-NMR experiments (1H NMR, 13C NMR, 1H- 1H NMR, HMQC, HMBC); as well as chemical derivative preparations. The relative stereochemistries of the methine protons around the tetrahydrofuran ring(s) were determined by comparison with compounds of known stereochemistry and with synthetic models. Where possible, the absolute stereochemistry of the carbinol centers were established by preparing the Mosher esters. All of the new compounds have been tested for their in vitro antitumor activities in a panel of six human solid tumor cell lines (A-549, MCF-7, HT-29, A-498, PC-3, and PACA-2), and some of them showed ED 50 values that are not only potent but are selective as well. This potent selectivity in different cancerous cell lines suggests that these compounds do not kill tumor cells through general cytotoxicity.
Degree
Ph.D.
Advisors
McLaughlin, Purdue University.
Subject Area
Medicine|Organic chemistry
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