The Ascidian-Derived Metabolites with Antimicrobial Properties

Abstract

Among the sub-phylum of Tunicate, ascidians represent the most abundant class of marine invertebrates, with 3000 species by heterogeneous habitat, that is, from shallow water to deep sea, already reported. The chemistry of these sessile filter-feeding organisms is an attractive reservoir of varied and peculiar bioactive compounds. Most secondary metabolites isolated from ascidians stand out for their potential as putative therapeutic agents in the treatment of several illnesses like microbial infections. In this review, we present and discuss the antibacterial activity shown by the main groups of ascidian-derived products, such as sulfur-containing compounds, meroterpenes, alkaloids, peptides, furanones, and their derivatives. Moreover, the direct evidence of a symbiotic association between marine ascidians and microorganisms shed light on the real producers of many extremely potent marine natural compounds. Hence, we also report the antibacterial potential, joined to antifungal and antiviral activity, of metabolites isolated from ascidian-associate microorganisms by culture-dependent methods.

Keywords: antibacterial; antimicrobial; antiviral; ascidian; ascidian-associated microorganisms; marine natural products.

Figure 1

(A) Percentage distribution of microorganisms paired to ascidians from which marine metabolites derive; (B) bioactivities of secondary metabolites isolated from ascidian-associated microorganisms described as percentage distribution.

Figure 2

Structures of the antimicrobial polysulfides lissoclinotoxins (1–2), varacins (3–6), and namenamicin (7).

Figure 3

Structures of alkyl and alkenyl sulfates 8–11.

Figure 4

Structures of the geranylhydroquinone derivatives 12–16 and of rossinones (17–21).

Figure 5

Structures of the amino alcohols crucigasterins (22–26), pseudoaminols (27–33), (2S, 3R)-2-aminododecan-3-ol (34), and distaminolyne A (35).

Figure 6

Structures of didemnaketals D–G (36–39).

Figure 7

Structures of the peptide-like compounds halocyamines (40 and 41), and of rodriguesines A and B (42 and 43).

Figure 8

Structures of the β-carbolines alkaloids eudistomins (44–66), 7-Bromo-N-hydroxyhomotrypargine (67), and didemnolines A–D (68–71).

Figure 9

Structures of the pyridoacridine alkaloids 72–88.

Figure 10

Structures of the indolizine alkaloids piclavines (89–91).

Figure 11

Structures of the guanidine alkaloids tubastrine (92), 3-dehydroxy tubastrine (93), and synoxazolidinones A–C (94–96).

Figure 12

Structures of the furanone derivatives rubrolides A–H, J, P, and Q (97–111) and cadiolides B–N (112–124).

Figure 13

Structures of synoilides A (125) and B (126) and isocadiolides A–H (127–134).

Figure 14

Structures of compounds 135–145 derived from ascidian-associated actinobacteria.

Figure 15

Structures of compounds 146–157 derived from ascidian-associated fungi.

Figure 16

Structures of the cyanobacteria-derived bisanthraquinones 1 and 2 (158 and 159).