Novel anti-cancer and pesticidal components from Asimina longfolia (Annonaceae)
Abstract
During our broad screening for bioactive plants, the leaves and twigs of the long leafed paw paw tree, Asimina longifolia K. (Annonaceae), were found to exhibit potent activity in the brine shrimp lethality test (BST). Subsequent bioactivity-directed investigation of the ethanol extract of the plant materials led to the isolation of twenty-one (1-21) bioactive components, eighteen of these (1-18) are Annonaceous acetogenins. Twelve of these acetogenins are new to the literature, and the known compounds were isolated for the first time from this species. An unusual fatty acid (21) and two known bioactive Annonaceous styrylactones (19, 20) were also isolated, and it is the first report of the presence of styrylactones in the genus Asimina. The structures of the novel acetogenins were determined by spectral analysis including UV; IR; low and high resolution CIMS, EIMS, and FABMS; and 1D and 2D-NMR experiments (COSY, relayed COSY, HMQC, HMBC, and NOESY) before and after certain chemical derivatizations. The relative stereochemistries between the methine protons around the tetrahydrofuran rings were established by careful analyses and comparisons of the $\rm\sp1H$ NMR spectra of acetate derivatives of these natural compounds with those of a series of model compounds. The absolute configurations of the carbinol centers were established by Mosher ester methods. All of the isolated natural compounds showed significant bioactivity. The acetogenins (1-18) obviously showed much higher bioactivities than the non-acetogenin compounds (19-21). The acetogenins are very active in the BST, and they showed significant cytotoxicities against A-549 (human lung carcinoma), MCF-7 (human breast carcinoma), HT-29 (human colon adenocarcinoma), A-498 (human kidney carcinoma), PC-3 (human prostate adenocarcinoma) and PaCa-2 (human pancreatic carcinoma) cell lines in our seven-day MTT human solid tumor cytotoxicity tests. These cytotoxicities are comparable or favorable to those of the positive control compound, adriamycin.
Degree
Ph.D.
Advisors
McLaughlin, Purdue University.
Subject Area
Pharmacology|Agricultural chemicals
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