People - [ Faculty ]
Over the years, my group has broadly been interested in the synthesis of oxygen heterocycles, and we have developed novel routes to tetrahydrofurans, tetrahydropyrans, and spiroketals which have been documented in the chemical literature. Most recently, we have turned our attention to the synthesis of biologically-active flavonoids and related substances. There is an increasing interest in naturally-occurring polyphenols, largely because of their potential medicinal properties. The green tea extract epigallocatechin-3-gallate, for example, is currently undergoing phase I clinical trials as a potential cancer chemopreventive agent for prostate and breast cancer. Similar compounds have been shown to be inhibitors of HIV 1 replication in vitro, and viral reverse transcription, while a specific trimeric procyanidin in cranberries has been shown to fight urinary infections by preventing E. coli from sticking to the cells that line the urinary tract.
Isolated from the root of Stellera chamaejasme L., a traditional Chinese herb, isochamaejasmine was found to alter several cell-signaling pathways, which could explain its use in the treatment of solid tumors, as well as tuberculosis. It has also been found to be active against several tumor cell lines including human myeloid leukemia cells. Structurally-related analogues of this compound have demonstrated antimalarial activity. A close relative of this compound, chamaejasmine, has been shown to possess both anti-inflammatory activity and aldose reductase inhibiting activity, suggesting that it could be a potential treatment for the complications associated with diabetic neuropathy. Efforts are currently underway in our lab to design synthetic routes to each of these natural products.
Anthocyanidins represent another class of compounds we are interested in. They are responsible for the characteristic dark pigmentations of several members of the plant kingdom, and they bestow several human health benefits, due largely to their antioxidant capacities. Very recently, for example, cyanidin-3-rutinoside, an extract of black raspberries, has been shown to kill leukemic cells in vitro while leaving healthy cells unharmed. Moreover, studies at the molecular level have revealed that anthocyanidins exert their cancer chemopreventive activity by several different mechanisms. This includes targeting and disrupting key cell-signaling pathways necessary for cell proliferation, suppressing inflammation by inhibiting the genetic expression of pro-inflammatory cytokines, and inducing cancer cell apoptosis by activating specific reactive oxygen species.