Date of Award
8-2010
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Legacy Department
Food Technology
Committee Chair/Advisor
Chen, Feng
Committee Member
Wang , Xi
Committee Member
Adelberg , Jeff
Committee Member
Kitaygorodskiy , Alex
Abstract
Gossypol is a naturally occurring, highly colored yellow pigment indigenous to the small intercellular pigment glands of the cotton plant genus Gossypium, which is proposed to be part of plant's defense system. Gossypol is characterized by wide contraceptive, antiviral, anticancer and antifungal properties. However, the relatively high toxicity of gossypol precludes its application in medical therapy. For this reason the syntheses and tests of gossypol derivatives, have been tried to enable their application as drugs. In our study, gossypol based methylation, glycosylation and nanoconjugate reactions were explored. The gossypol derivatives were all fully characterized by NMR, MS, FT-IR, UV spectrometry, HPLC and X-ray crystallography. Firstly, hexamethyl ethers of gossypol were synthesized, particularly, existence of four tautomers of gossypol tetramethyl ethers were chromatographically separated and confirmed. Gossypol exhibited the strongest antioxidant activity, while its ethers only remained partial antioxidant activity due to their conjugated naphthalene structure preserved in the derivatives. The result of alpha-amylase inhibitory activities of gossypol and its methylated ethers showed that the gossypol's methylated ethers were the alpha-amylase inhibitors, while gossypol was the alpha-amylase activator. Furthermore, it was found that anticancer activity of the gossypol and its methylated ethers depended on the degree of methylation level of gossypol. Secondly, novel glycosidic gossypol analogues were obtained by the ultrasound-assisted reaction of potassium salt of gossypol with 3, 4, 6-tetra-O-acetyl-α-D-glucopyranosyl bromide under phase transfer catalytic condition. The evaluation of anticancer, antitrypanosomal activities as well as cytotoxicity of those novel glycosidic gossypol derivatives implied that 6, 7'-gossypol diglycosidic tetraacetate (compound 8) could be developed into a potential pharmaceutical candidate in the treatment of cancer since it exhibited powerful cancer cells inhibition with significantly low cytotoxicity. In addition, 7, 7'-gossypol diglycosidic tetraacetate (compound 7) and 6, 7'- gossypol diglycosidic tetraacetate (compound 8) possess antitrypanosomal activity with LD50 value of 2.12 and 2.44 µM, respectively. Finally, gossypol reacted with fullerene [60] in the presence of sarcosine through the Prato reaction, resulting in some unexpected N-methylfulleropyrrolidines, and different products in variable yields were obtained when choosing toluene or chlorobenzene as reaction medium. During the reaction, gossypol decomposed into benzaldehyde which was successfully detected as a new intermediate. In an in vitro assay of NO radical induced apoptosis in 3T3L1 cells for the N-methyl-2, 2-dimethylfulleropyrrolidine (compound 14) showed dose dependent and stronger radical scavenging activities than the parent fullerene.
Recommended Citation
Yin, Juanjuan, "CHEMICAL MODIFICATION AND BIOLOGICAL ACTIVITY EXPLORATION OF THE NATURAL PRODUCT-GOSSYPOL" (2010). All Dissertations. 598.
https://open.clemson.edu/all_dissertations/598