Diterpenes for Therapeutic Use

Abstract

Diterpenes are a structurally diverse class of C₂₀ natural compounds, widely distributed in nature and originating by condensation of four isoprene units derived from mevalonate or deoxyxylulose phosphate pathways. The latter, recently discovered, originates the diterpene compounds in plants. Diterpenes can be classified as linear, bicyclic, tricyclic or tetracyclic, pentacyclic, and macrocyclic diterpenes depending on their skeletal core. In nature, they are commonly found in a polyoxygenated form with keto and hydroxyl groups, these last often esterified by small-sized aliphatic or aromatic acids.

Diterpenes have attracted growing attention because of their interesting biological and pharmacological activities. Although thousands of diterpene compounds have been described in nature from terrestrial and marine organisms, only few of them became clinically effective. Overall, the anticancer drug taxol, used in therapy against ovarian, breast, and lung cancer, with its synthetic water-soluble analogue taxotere, is an example of unusual structure discovered from nature and used as medicine. Promising diterpenes are the ginkgolides showing potent and selective antagonistic activity toward platelet-activating factor increasing in conditions of shock, burns, ulceration, and inflammation skin diseases. Also used in therapy is the diterpene resiniferatoxin, an ultrapotent vanilloid, isolated from the Euphorbia resinifera latex, in clinical trials for bladder hyperiflexia and diabetic neuropathy. The diterpenes used in therapy will be described together with other promising bioactive diterpenes with particular attention to those isolated from plants.