Thesis (Ph.D.)--Chulalongkorn University, 2014

Oxyresveratrol, or 2,3′,4,5′-tetrahydroxystilbene, is a secondary metabolite found in large amounts in the heartwood of Artocarpus lakoocha Roxb. (Moraceae). Because of the wide range of potential biological activities, together with the easy extractability from the plant material, oxyresveratrol was chosen as a lead structure for chemical modification in an attempt to prepare polyoxygenated stilbenes with higher potency and selective activity. In this study, several types of reactions were carried out, including O-alkylation, O-acylation and aromatic substitution. As a result, a total of twenty-six derivatives were prepared. Biological studies of these semi-synthetic products were conducted, in comparison with the parent compound, to investigate their DNA protective activity, and their inhibitory activity against the herpes simplex virus and the enzyme avian influenza neuraminidase. In addition, these compounds were further evaluated for their anti-α-glucosidase activity and cytotoxicity against selected cancer cells. In this study, a new assay for DNA protective activity was developed and then applied on oxyresveratrol and its semisynthetic analogues. Oxyresveratrol was found to possess stronger DNA protective activity than Trolox and ascorbic acid. Sixteen of the prepared analogues showed activity even higher than the parent compound, with an 7-fold increase of the activity observed for the most potent compound, 2,4,3′-tri-O-methyloxyresveratrol. This same compound was also the strongest analogue against herpes simplex virus; it was about 4-time as strong as oxyresveratrol. Three other derivatives were also found to possess enhanced anti-HSV activity. Regarding the inhibitory activity on the enzyme neuraminidase, only 5-carboxyoxyresveratrol exhibited activity close to that of the precursor, whereas the others were less active. Concerning the cytotoxicity against cancer cells, sixteen and ten oxyresveratrol derivatives were active against KB and MCF-7 cells, respectively. 3′,5′-O-Diacetyl-2,4-di-O-isopropoyloxyresveratrol was the most cytotoxic compound against KB cells, while 2,4,3′-tri-O-isopropyloxyresveratrol was the most potent against MCF-7 cells. Interestingly, the latter was also found to have anti-α-glucosidase activity approximately equal to that of oxyresveratrol.