Recent developments towards podophyllotoxin congeners as potential apoptosis inducers

Podophyllotoxin, a lignan extracted from rhizomes of Podophyllum species, is a well established lead in the development of new chemical agents for the treatment of cancer. Its semi-synthetic variant, etoposide is an anticancer drug which inhibits DNA topoisomerase II causing cell cycle arrest in the S the phase. Its clinical success and intriguing mode of action made it a much sought after skeleton for the development of better antitumor agents. Modifications were made at several positions of its skeleton with the aim to either improve its potency or to overcome drug resistance. In recent years, the structurally modified podophyllotoxins have been investigated for their apoptosis inducing ability. Although numerous reviews emphasized the occurrence, synthesis and applications of podophyllotoxins, the recent progress towards development of structurally modified podophyllotoxins possessing apoptosis inducing ability has not been previously reviewed. Therefore the present review focuses on the studies carried out in the design and synthesis of new podophyllotoxin derivatives and their evaluation as apoptosis inducers.