SYNTHESIS OF PODOPHYLLOTOXIN CONGENERS AS POTENTIAL DNA TOPOISOMERASE-II INHIBITORS

We have synthesized a number of new podophyllotoxin congeners in which the A-ring is opened and the C-ring is aromatic. These are based on t he chemically modified structures of the naturally occurring podophyll um lignan, diphyllin. These have been synthesized by employing the Mic hael Initiated Ring Closure methodology. These lignans exhibited consi derable DNA topoisomerase II inhibition and were devoid of topoisomera se I inhibition; they did not exhibit very significant activities in t he in vitro human tumour cell lines assay. The results obtained provid e insights into the structure-activity relationships and the design of chemically modified podophyllo-toxin congeners useful in cancer chemo therapy.