Potent anti-tumor and anti-inflammatory lead structures from Caribbean sponges

Marine natural products are playing an increasingly important role in biomedical research and drug discovery, either directly as drugs or as lead structures. Caribbean marine sponges are well-known to produce a large array of new chemical structures with promising anti-cancer, anti-inflammatory, immunomodulating and anti-bacterial properties. Over the last 15 years our research group’s interest has been focused on the chemical study of these colorful animals living in the tropical oceans as a source of new structures to be used as leads in the search of new drugs. Two topics of our ongoing research work will be discussed in the communication: a. the antinflammatory activity of tedanol, a new brominated and sulphated diterpene alcohol having a pimarane skeleton, which was isolated from the Caribbean sponge T. ignis. Tedanol showed a significant anti-inflammatory in vivo activity at 1 mg/kg, coupled with the inhibition of the COX-2 expression. This activity makes tedanol a novel potent COX-2 selective inhibitor, and could represent an excellent water-soluble antiinflammatory molecule with minimal gastrointestinal toxicity. b. The anti-tumor activity of three diterpene isonitriles isolated from the Caribbean sponge Pseudaxinella flava. The compounds have been first screened for their in vitro growth inhibitory activity (MTT assay) using the four human cell lines. Then, the gross mechanism of action of the isonitriles have been determined by means of computer-assisted phase contrast videomicroscopy analysis. The digital movies showed that the cancer cells treated with isonitriles are pro-autophagic agents and make the cells unable to undergo mitotic processes, resulting in a cytostatic effect.