Structural modifications of plumieride isolated from Plumeria bicolor and the effect of these modifications on in vitro anticancer activity.

Mahabeer P Dobhal, Guolin Li, Amy Gryshuk, Andrew Graham, Atul K Bhatanager, Sirajud D Khaja, Yogesh C Joshi, Mahesh C Sharma, Allan Oseroff, Ravindra K Pandey

Index: J. Org. Chem. 69(19) , 6165-72, (2004)

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Abstract

Plumieride was isolated as one of the major components from the biologically active methanolic extract of the bark of Plumeria bicolor (family Apocynaceae). For investigating the effect of substituents on cytotoxic activity it was modified into a series of compounds. Replacing the methyl ester functionality of plumieride with alkyl amides of variable carbon units improved the cytotoxic activity, and a correlation between overall lipophilicity and cytotoxic activity was observed. In plumieride, the glucose moiety was converted into a di- and trisaccharide by following the protection and deprotection approach, and the resulting compounds produced enhanced cytotoxicity. However, these compounds were found to be less effective than plumeiride containing a dodecyl (12 carbon units) amide group. Among all of the derivatives, the naturally occurring plumieride showed the least cytotoxicity (50% cell kill = 49.5 microg/mL), and the dodecyl amide analogue of plumieridepentaacetate produced the best efficacy (50% cell kill = 11.8 microg/mL). The di- and trisaccharide analogues were found to be slightly less effective than the dodecyl derivative (50% cell kill = 15-17 microg/mL). The in vitro cytotoxicity of the plumieride analogues was determined in radiation-induced fibrosarcoma (RIF) tumor cells.