Synthesis of the Marine Pyrroloiminoquinone Alkaloids, Discorhabdins

  title={Synthesis of the Marine Pyrroloiminoquinone Alkaloids, Discorhabdins},
  author={Yasufumi Wada and Hiromichi Fujioka and Yasuyuki Kita},
  journal={Marine Drugs},
  pages={1394 - 1416}
Many natural products with biologically interesting structures have been isolated from marine animals and plants such as sponges, corals, worms, etc. Some of them are discorhabdin alkaloids. The discorhabdin alkaloids (discorhabdin A-X), isolated from marine sponges, have a unique structure with azacarbocyclic spirocyclohexanone and pyrroloiminoquinone units. Due to their prominent potent antitumor activity, discorhabdins have attracted considerable attention. Many studies have been reported… 

Figures from this paper

Dactylospongia elegans—A Promising Drug Source: Metabolites, Bioactivities, Biosynthesis, Synthesis, and Structural-Activity Relationship

Reviewing the reported metabolites from D. elegans revealed that these metabolites could contribute to new drug discovery, however, further mechanistic and in vivo studies of these metabolites are needed.

Discovery and development of synthetic tricyclic pyrroloquinone (TPQ) alkaloid analogs for human cancer therapy

It is successfully demonstrated that these makaluvamines attack several key molecular targets, including the MDM2-p53 pathway, providing ample opportunities of modulating the compound structure based on SAR and the use of such compounds in combination therapy in the future.

Synthesis, in vitro and in silico studies of indolequinone derivatives against clinically relevant bacterial pathogens.

3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative is highlighted as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections.

Synthetic Strategies for 5- and 6-Membered Ring Azaheterocycles Facilitated by Iminyl Radicals

The search for fast, efficient and environmentally friendly preparative methods for these rings with specific emphasis on iminyl radical-mediated procedures for Pyrrole, indole, pyridine,Quinoline, quinazoline and related 6-membered ring-containing aza-arenes figure prominently.

Preclinical Evaluation of Discorhabdins in Antiangiogenic and Antitumor Models

It is demonstrated that only discorhabdin L (2) possesses excellent anti-angiogenic activity in inhibiting endothelial cell proliferation and tube formation, as well as decreasing microvessel outgrowth in the ex vivo rat aortic ring assay.

Recent advances in deep-sea natural products.

Most strikingly, 75% of the compounds were reported to possess bioactivity, with almost half exhibiting low micromolar cytotoxicity towards a range of human cancer cell lines, along with a significant increase in the number of microbial deep-sea natural products reported.

Discorhabdins and pyrroloiminoquinone-related alkaloids.

Discorhabdins and Pyrroloiminoquinone-Related Alkaloids and their applications in Brain Functional Genomics and Drug Discovery are proposed.



Antitumor activity and distribution of pyrroloiminoquinones in the sponge genus Zyzzya.

Novel cytotoxic topoisomerase II inhibiting pyrroloiminoquinones from Fijian sponges of the genus Zyzzya

The structure determination of the new compounds are reported and preliminary evidence for the ability of this class of metabolites to inhibit the function of mammalian topoisomerase 119 and to inhibits the growth of human ovarian tumor in an athymic mouse model is reported.

Synthesis of antitumor marine alkaloid discorhabdin A oxa analogues.

The synthesis and examination of the biological activity of various types of stable discorhabdin A oxa analogues, which also have strong cytotoxic activity and stability, were achieved.

Discorhabdins revisited: cytotoxic alkaloids from southern australian marine sponges of the genera Higginsia and Spongosorites.

Chemical analysis of southern Australian marine sponges of the genera Higginsia and Spongosorites has yielded examples of the discorhabdin class of alkaloids. These include the known metabolites

Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges.

The anticancer activity of 20 pyrroloiminoquinone compounds was explored in the HCT-116 cancer cell line screen, and the DNA intercalation of the tsitsikammamines, together with their ability to cleave DNA through topoisomerase I inhibition, is discussed.

The first total synthesis of discorhabdin A.

These methodologies provide a breakthrough in the total syntheses of these promising new antitumor agents, discorhabdins and their analogues, which should serve as valuable probes for structure-activity studies.

A Biomimetic Approach to the Discorhabdin Alkaloids: Total Syntheses of Discorhabdins C and E and Dethiadiscorhabdin D.

The characteristic spirodienone structure of the discorhabdin alkaloids is readily formed by reaction of the tyramine-substituted indoloquinonimines 26, 35, and 36 with cupric chloride,

Biomedical Potential of Marine Natural Products

The intent of this chapter is to look back at the evolution of biomedically oriented natural product studies of marine organisms, to chronicle the key developments, discoveries, and advances in the level of sophistication that have fueled further interest in this field, and to look forward at the future biomedical potential of marine natural products.

Analogues of marine pyrroloiminoquinone alkaloids: synthesis and antitumor properties.

  • E. Delfourne
  • Chemistry
    Anti-cancer agents in medicinal chemistry
  • 2008
This review focuses on synthesis and antitumor evaluation of analogues of iminoquinone alkaloids including makaluvamines, isobatzellines, tsitsikammamines and wakayin.