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[摘要]：Sixteen analogs of the unique flavonoid desmosdumotin B were prepd. and evaluated as in vitro inhibitors of the human KB cancer cell line and its MDR subclone, KB-VIN. 6,8,8-Tri-Et analogs showed enhanced showed significant ED50 values of 0.03 and 0.025 mg/mL, resp., against KB-VIN with selectivities of >460- and 320-fold compared with that of KB. This report is the first to describe compds. showing such high activity against MDR cells vs. non-MDR cells. The unique activity of the desmosdumotin B analogs is likely MDR-mediated because cotreatment with verapamil, a P-gp inhibitor, partially reversed the selective toxicity of both desmosdumotin B and III. Interestingly, only the desmosdumotin B analogs with a naphthalene B-ring showed significant cytotoxic activity against KB and other cancer cell lines. Thus, the synthesized analogs might be a new class of potent drug candidates, esp. as I and II express direct selective action against tumors expressing MDR. |
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