RELATIVE CONTRIBUTIONS TO ANTITUMORAL ACTIVITY OF LIPOPHILIC VS POLARREACTIVE MOIETIES IN MARINE TERPENOIDS

Marked cytotoxicity of norsesterterpenoids 3 and 4 vs. inactivity or l ow 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 functional ity is not. Moreover, lower bioactivity towards the same cells of 1 th an 2, and comparable activities of 3-5, show the unimportance per se o f the highly electrophilic enone moiety. A strict need of molecular ta iloring, so that weapons may reach the target in adaptive phenomena, m ay be at the basis of natural selection of these compounds and suggest s strategies for the design of safer agents against cancer. (C) 1997 E lsevier Science Ltd.