The Xing lab has explored CXL compounds as cytotoxic anticancer agents in multi-drug resistant leukemic cell lines. CXL compounds have exhibited an increased potency in drug resistant cell lines compared to their parental cell lines. CXL compounds act through the inhibition of the sarco-endoplasmic reticulum calcium ATPase (SERCA). SERCA inhibition causes cell death through an increase in cytosolic calcium levels, ER stress, and triggering the unfolded protein response. The binding site of CXL compounds on SERCA and the identity of other cellular targets have been investigated through photoaffinity labeling with probes CXL039 and CXL037 respectively. Alterations in the synthesis of CXL compounds were also examined to improve the overall yield. Compounds that exhibit the same cytotoxicity profile as CXL compounds were explored through a cell based screen of natural products in HL60 and HL60 doxorubicin resistant cells.
University of Minnesota M.S. thesis. April 2016. Major: Medicinal Chemistry. Advisor: CHENGGUO XING. 1 computer file (PDF); x, 74 pages.
Analyses Of Detoxification And DNA Damage From The Human Carcinogens Benzene And N′-Nitrosonornicotine.
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