Secondary Metabolites of the Genus Didemnum: A Comprehensive Review of Chemical Diversity and Pharmacological Properties

Abstract

Tunicates (ascidians) are common marine invertebrates that are an exceptionally important source of natural products with biomedical and pharmaceutical applications, including compounds that are used clinically in cancers. Among tunicates, the genus Didemnum is important because it includes the most species, and it belongs to the most speciose family (Didemnidae). The genus Didemnum includes the species D. molle, D. chartaceum, D. albopunctatum, and D. obscurum, as well as others, which are well known for their chemically diverse secondary metabolites. To date, investigators have reported secondary metabolites, usually including bioactivity data, for at least 69 members of the genus Didemnum, leading to isolation of 212 compounds. Many of these compounds exhibit valuable biological activities in assays targeting cancers, bacteria, fungi, viruses, protozoans, and the central nervous system. This review highlights compounds isolated from genus Didemnum through December 2019. Chemical diversity, pharmacological activities, geographical locations, and applied chemical methods are described.

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

“…Typically, most ascidian compounds contain one or two heteroatoms, most frequently nitrogen and/or oxygen and occasionally sulfur, that are presumably derived from amino acids and many of these are biologically active [6,7]. The lepadin family, comprising, until now, eleven decahydroquinoline members, was identified from ascidians belonging to the genera Clavelina, Didemnum, and Aplidium as well as their predators [8][9][10][11][12]. These secondary metabolites are characterized by 5-alkyl-3-hydroxydehydroquinoline nucleus with a diversified array of relative stereochemical relationships at C-2, C-3, C-4a, C-5, and C-8a (Figure 1).…”

Anti-tumour drugs of marine origin currently at various stages of clinical trials (review)

“…In the period from 1994 to 2014, from ascidians, there were isolated 580 compounds with antibacterial, anti-inflammatory, anti-virulent, anti-diabetes, anti-proliferative, anti-parasitic activities (Palanisamy et al, 2017). Currently, the most efficient producers of biologically active compounds are considered the representatives of the Didemnidae, Polyclinidae and Polycitoridae families, and out of 69 representatives of Didemnum genus, there were isolated 212 biologically active compounds (Diaa et al, 2020). The high pharmacological potential of nonribosomal peptides, proline-rich cyclic peptides and many compounds of various chemical classes produced by ascidians, and clinical application of them for the treatment of broad range of diseases, including in oncology, are well known (Diaa et al, 2020).…”

“…Currently, the most efficient producers of biologically active compounds are considered the representatives of the Didemnidae, Polyclinidae and Polycitoridae families, and out of 69 representatives of Didemnum genus, there were isolated 212 biologically active compounds (Diaa et al, 2020). The high pharmacological potential of nonribosomal peptides, proline-rich cyclic peptides and many compounds of various chemical classes produced by ascidians, and clinical application of them for the treatment of broad range of diseases, including in oncology, are well known (Diaa et al, 2020). In experiments, toxic metabolites of ascidians exerted effects on DNA transcription, protein translation, processes of neurohumoral regulation, cytoskeleton (Agrawal et al, 2016;Fang et al, 2016;Negi et al, 2017;Arumugam, 2018).…”

Hemimycalins C–E; Cytotoxic and Antimicrobial Alkaloids with Hydantoin and 2-Iminoimidazolidin-4-one Backbones from the Red Sea Marine Sponge Hemimycale sp.

“…Since 1963, more than 30,000 new chemical entities have been identified from marine organisms, including macroand micro-organisms [3]. Secondary metabolites obtained from marine invertebrates have received great attention from pharmacologists and chemists due to their remarkable chemical diversity and biological activities [4][5][6]. The fact that 14 marine-derived approved drugs and another 23 drug leads in different phases (I-III) of clinical trials [7], mostly from marine invertebrates [7], clearly indicates the role of marine invertebrates as a vigorous source for the drug-discovery process [7].…”