Chemists working at the Sandoz pharmaceutical company developed the hypothesis that podophyllin resin may contain anticancer lignan glycosides that are more water-soluble and less toxic than podophyllotoxin, and several of these natural products were isolated. The compounds did indeed possess greater water solubility but unfortunately less antitumour activity. Much work was done on these glycosides to make them resistant to enzymic hydrolysis, maintain their water solubility and improve their cellular uptake. This was a difficult task as, paradoxically, improving the water solubility decreased the cellular uptake (and therefore activity)