Date of Award

12-2008

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Food Technology

Advisor

Chen, Feng

Committee Member

Xi , Wang

Committee Member

Marcus , R. Kenneth

Committee Member

Kitaygorodskiy , Alex

Abstract

ABSTRACT
African mahogany Khaya senegalensis (Desr.) A. Juss (Meliaceae) is a large tree growing mainly in the sub-Saharan savannah forests from Senegal to Uganda. This plant is one of the most popular medicinal meliaceous plants in traditional African remedies, used as a bitter tonic, folk and popular medicine against malaria, fever, mucous diarrhea, and venereal diseases as well as an anthelmintic and a taeniacide remedy. Its extracts and chemical constituents have been the subject of extensive phytochemical and pharmacological investigations since 1960s. Anti-inflammatory, anti-bacterial, anthelmintic, and antiplasmodial activities of plant extracts have been reported. Limonoids with anti-feeding, feeding deterrent and growth inhibitory properties, anti-fungal, and anti-sickling activity, as well as dimeric flavonoids with immunostimulating activity have been isolated from different parts of this plant. However, none of extracts or pure chemicals has been screened for biological activity such as antioxidant activity and anti-proliferative capacity against human cancer cell lines. Therefore, the main object of this study was to screen bioactive ingredients with anticancer and antioxidant activities from the plant through purification, isolation, structural elucidation, and bioassays.
Eleven natural products were isolated from the methanolic extract of stem bark of Khaya senegalensis after extraction and purification, especially through crystallization and modern column chromatographic techniques using normal phase and reverse phase silica gel columns, Sephadex LH-20, MCI CHP20P, prep-HPLC, etc. Their structures were determined to be two ring D-seco limonoids 3, 7-dideacetylkhivorin (1) and 1, 3, 7-trideacetylkhivorin (2), mexicanoloid limonoid khayanone (3), five khayanolide limonoids 1-O-deacetylkhayanolide B (4), khayanolide B (5), khayanolide E (6), 1-O-deacetylkhayanolide E (7), and novel 6-dehydroxykhayanolide E (8), three lignans (-)-lyoniresinol (9), (-)-lyoniresin-9-yl-D-xylopyranoside (10), and (-)-lyoniresin-4'-yl-D-glucopyranoside (11), respectively, through various spectroscopic methods including IR, EI-MS (HREI-MS), LC-ESI-MS (accurate ESI-MS), extensive 1D and 2D NMR (1H , 13C, DEPT, 1H-1H COSY, HMQC or HSQC, HMBC, NOESY), and X-ray diffraction experiments.
The structures and stereochemistry of 1, 2, 3, 4, 6, and 8 were confirmed through X-ray crystallography. Based on the X-ray diffraction analyses and NMR data, two reported khayanolides 12 and 13 are, in fact, 1-O-acetylkhayanolide B 4 and khayanolide B 5, respectively, and two reported phragmalins 14 and 15 are, in fact, khayanolide E 6 and 1-O-deacetylkhayanolide E 7, respectively.
In the anti-proliferative bioassay, 1 and 2 showed significant growth inhibitory activities against MCF-7, SiHa, and Caco-2 tumor cells with IC50 values in the range of 35-69 microgram/ml, while other compounds did not show anticancer activity even at high concentration 200 microgram/ml; 9, 10, 11 exhibited strong antioxidant activities comparable to that of BHT, regarding the DPPH free scavenging activity.

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