Abstract
Forty-one derivatives of papyriferic acid were prepared based on our previous finding that methyl papyriferate ( 3) showed potent reversing effect on cytotoxicity of colchicine against multidrug resistance (MDR) human cancer cells (KB-C2), and evaluated for their cytotoxicity and effect on reversing P-gp-mediated MDR against KB-C2 cells. 3- O-(Morpholino-β-oxopropanoyl)-12β-acetoxy-3α,25-dihydroxy-(20 S,24 R)-epoxydammarane ( 37) significantly increased the sensitivity of colchicine against KB-C2 cells by 185-fold at 5 μg/mL (7.4 μM), and the cytotoxicity of colchicine was recovered to nearly that of sensitive (KB) cells. The other several new amide derivatives also exhibited potent reversal activity comparable to or more potent than methyl papyriferate and verapamil.
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