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Antitumor compounds from tunicates.

¹Department of Chemistry, University of Illinois, 454 Roger Adams Laboratory, 600 So. Mathews Avenue, Urbana, Illinois 61801, USA.

Medicinal Research Reviews

|December 23, 1999

Summary

Marine-derived tunicates yield potent antitumor compounds. Didemnin B showed promise but caused cardiotoxicity; its analogue, Aplidine, is in clinical trials. Ecteinascidins are also under investigation.

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Area of Science:

Marine pharmacology
Natural product chemistry
Antitumor drug development

Background:

Tunicates are a rich source of marine-derived compounds with antitumor potential.
Didemnin B (DB) and Ecteinascidins (ETs) are two families of tunicate-derived compounds that have advanced to clinical trials.
DB showed efficacy in non-Hodgkins lymphoma but was discontinued due to cardiotoxicity.

Purpose of the Study:

To review marine-derived antitumor agents from tunicates.
To highlight the development of Didemnin B, Aplidine, and Ecteinascidin 743.
To discuss the potential of these compounds in cancer therapy.

Main Methods:

Review of clinical trial data and spectroscopic studies.
Isolation and structural elucidation of marine natural products.
Synthesis and chemical modification of bioactive compounds.

Main Results:

Didemnin B (DB) demonstrated efficacy but exhibited cardiotoxicity.
Aplidine (dehydrodidemnin B), a related compound, shows improved activity and reduced toxicity, entering Phase I trials.
Ecteinascidin 743 (ET 743) is undergoing Phase II clinical trials, with potential for aquaculture or synthetic production.

Conclusions:

Tunicate-derived compounds like Aplidine and Ecteinascidin 743 represent promising avenues for cancer treatment.
Overcoming toxicity and ensuring supply through synthesis or aquaculture are key for future development.
Marine natural products continue to be a vital resource for novel anticancer drug discovery.

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