Two classes of bioactive constituents: Annonaceous acetogenins and styryllactones from Goniothalamus giganteus (Annonaceae)
Abstract
The goal of this project has been to find novel antitumor leads from Goniothalamus giganteus Hook. f. & Thomas (Annonaceae); the ethanol extract of the bark showed in vivo and in vitro antitumor activities. Under the direction of a simple bioassay, the brine shrimp lethality test (BST), we have isolated six new (1-6) and one known (7) highly cytotoxic Annonaceous acetogenins and ten novel (8-17) and one known (18) moderately cytotoxic styryllactones from the bark. The structures of these compounds were elucidated by making chemical derivatives, using extensive spectral methods, such as MS, $\sp1$H and $\sp{13}$C NMR, COSY, relayed COSY, HETCOR, HMQC, HMBC, NOESY, and NOE difference spectra, and applying X-ray crystallographic analyses. The cytotoxicities (seven-day test) of the seven acetogenins against three common human solid tumor cell lines (A-549, MCF-7, and HT-29) ranged from ED$\sb{50}$ values of 8 down to 6 $\times$ 10$\sp{-8}$ $\mu$g/ml and showed certain selectivities. Among the new acetogenins, gigantetrocin (1) is one of the first reported acetogenins with a vicinal diol moiety along the aliphatic chain, giganenin (2) is the first acetogenin found containing an isolated double bond on the chain, gigantetronenin (4) and gigantrionenin (5) have both vicinal diol and double bond moieties, and giganin (6) is the first acetogenin without any ring along the aliphatic chain. 4-Deoxygigantecin (3) is a new non-adjacent bis-THF acetogenin. These vicinal diol or/and double bond containing acetogenins strongly support the previously proposed polyketide origin of the Annonaceous acetogenins, and a possible biogenetic pathway for the acetogenins isolated from G. giganteus has been proposed. The eleven styryllactones isolated showed modest or marginal cytotoxicities to the three human tumor cell lines. Among these styryllactones, the X-ray crystal structures of goniofufurone (8), 7-epigoniofufurone (9), goniopypyrone (10), 9-deoxygoniopypyrone (11), and goniodiol (18) diacetate have been determined along with spectral data (NMR, MS, etc.). The structures of the other styryllactones, goniobutenolides A (13) and B (14), goniofupyrone (12), gonioheptolides A (15) and B (16), and 8-acetylgoniotriol (17), were mainly deduced from their chemical and spectral data. The biogenetic correlation of these compounds is predicted.
Degree
Ph.D.
Advisors
McLaughlin, Purdue University.
Subject Area
Pharmaceuticals|Pharmacology|Organic chemistry
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