SYNTHESIS AND CYTOTOXICITY OF NOVEL LIGNANS

In this study the syntheses of 11 novel lignans are described. Their c ytotoxicities are studied in GLC(4), a human small cell lung carcinoma cell line, using the microculture tetrazolium (MTT) assay. Ten of the se compounds were substituted with a menthyloxy group on the 5-positio n of the lactone. These compounds can easily be prepared in (novel) 'o ne-pot', three- or four-step syntheses. In addition, methods for contr olling the stereogenic centers are described. Furthermore, five natura lly occurring podophyllotoxin-related compounds were tested. The cytot oxicities of all lignan compounds, and of three non-lignan intermediat es originating from the syntheses, were compared with the clinically a pplied anticancer agents etoposide, teniposide, and cisplatin. Most co mpounds showed moderate to high activities against GLC(4), and two of the compounds containing a menthyloxy group showed activities comparab le to the reference cytotoxic agents.