Marine Diterpenoids as Potential Anti-Inflammatory Agents

Abstract

The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules.

Figure 1

Structures of klymollin G [1] and klymollin M [2]. The epoxy group at C-17 for klymollin G and phenylacetate group at C-6 are labeled.

Figure 2

Structures of briarellin S [3] and seco-briarellinone [4]. The opening of the 10-member ring and the presence of carbonyl groups in the seco-briarellinone that have been suggested as being responsible for the higher anti-inflammatory effect than briarellin S are labeled.

Figure 3

Structure of excavatolide B [5]. The 8,17-epoxide and 12-hydroxyl groups that have been suggested as being responsible for the anti-inflammatory effect are marked.

Figure 4

Cembrane diterpenoids: lobohedleolide [6], lobocrasol A [7], and sinumaximol B [8]. The presence of a α-methylene-γ-lactone in lobohedleolide (and cembranolides); an epoxy group at C-1/C-15 in lobocrasol A and a hydroxyl group at C-7 and/or C-8 in sinumaximol B are labeled.

Figure 5

Pseudopterosin A [9], elisabethadione [10], and elisabethatrienol [11]. Glycoside diterpene, pseudopterosin A, nonglycoside diterpenes, elisabethadione, and elisabethatrienol.

Figure 6

Pseudopterolide derivative [12] and isogorgiacerodiol [13]. The methoxyl group at C-9 in pseudopterolide derivative that has been suggested as being responsible for the higher anti-inflammatory effect than isogorgiacerodiol is labeled.