Relative contributions to antitumoral activity of lipophilic vs. polar reactive moieties in marine terpenoids

Marked cytotoxicity of norsesterterpenoids 3 and 4 vs. inactivity or low activity of the respective norditerpenoid analogues 2 and 1 towards KB tumoral cell lines suggest that the length of the lipophilic chain is an important factor while, per se the reactive peroxide functionality is not. Moreover, lower bioactivity towards the same cells of 1 than 2, and comparable activities of 3-5, show the unimportance per se of the highly electrophilic enone moiety. A strict need of molecular tailoring, so that weapons may reach the target in adaptive phenomena, may be at the basis of natural selection of these compounds and suggests strategies for the design of safer agents against cancer. (C) 1997 Elsevier Science Ltd.