INTRODUCTION
Marine gorgonian organisms are a prolific source of novel biologically active products called the pseudopterosins,
which exhibit a range of biomedical activities. For decades, extensive research on the psedopterosins has led to incremental advancements in documenting their biosynthetic and mechanistic pathways culminating in their classification as superior anti-inflammatory and analgesic agents. Discovery of their anti-inflammatory properties has led to studies examining their usefulness in various inflammatory conditions ranging from rheumatoid arthritis and asthma to psoriasis, contact dermatitis, photodamage, and dermatoheliosis, as well as HIV and cancer. Of interest, their anti-inflammatory and analgesic potencies have been shown to be superior to the industry standard indomethacin in a concentration and dose dependent fashion.1,3,4 Hence, the pseudopterosins hold promise as novel anti-inflammatory compounds and they may prove a viable alternative to conventional therapies in preventing and treating inflammatory disorders involving the skin and other organ systems.
BACKGROUND
The marine environment exists as an untapped resource of tremendous opportunities for current and future medical therapies.
The terpenes, the marine group of largest biological diversity consists of the pseudopterosins, which are an exemplary
example of the distinct biochemical properties that can be harnessed from marine organisms into innovative therapeutic
modalities. The pseudopterosins are novel structurally distinct biologically active metabolites of the Caribbean gorgonian
soft coral of the genus Pseudopterogorgia Elisabethae. P. Elisabethae is an octocoral found in the Caribbean waters of the Central Bahamas, Bermuda, and West Indies as well as the Florida keys. The seco-pseudopterosins, isolated from P. Kallos in the Florida Keys are close relatives of the pseudopterosins.2 To date, 26 derivatives of P. Elisabethae have been isolated (designated PsA-PsZ).
Despite their large number and chemical diversity, the pseudopterosins are structurally similar. That is, they all have a tricyclic diterpene core and their carbohydrate moiety (either fucose or xylose) is located at C9 or C10. They differ primarily in the degree of acetylation of their glycoside group and stereochemistry ie, the isobutenyl group at C1 can be alpha or beta (see diagram). However, there may still be measurable qualitative and quantitative differences between the pseudopterosins with respect to their biochemical profile likely relating to the marine habitat from which they are isolated. Collectively, these natural products are of great interest given their superior anti-inflammatory and analgesic properties as well as their antimicrobial and wound healing capabilities. Their attractiveness as a class of powerful anti-inflammatory compounds is largely related to their molecular structure, pharmacological mechanisms of action, and the absence of adverse effects, clearly separating them from the other well known anti-inflammatory therapies namely NSAIDS, selective COX2 inhibitors, and glucocorticosteroids.
How do the pseudopterosins work? Given the complexity of the inflammatory pathways, there are multiple levels at which a drug can have an effect on the inflammatory cascade. Most anti-inflammatory drugs target the arachidonic acid pathway which ends in the production of eicosanoids, specifically prostaglandins,prostacyclins, thromboxanes and leukotrienes, all critical mediators of the inflammatory response.
NSAIDS block prostaglandin synthesis via primary COX2 inhibition without targeting the leukotriene pathway. Glucocor-
