Didemnins

Didemnins are cyclodepsipeptide compounds isolated from a tunicate (sea-squirt) of the genus "Trididemnum" (family of Didemnidæ) that were collected in the Caribbean Sea. They were first isolated in 1978 at the University of Illinois. [Rinehart L., K. "et al.". "J. Am. Chem. Soc." 1981, "103", 1857-1859.]

Although more than nine Didemnins (Didemnins A-E, G, X and Y) have been isolated from the extract of "Trididemnum solidum", Didemnin B is the one that possesses the most potent biological activities. [Rinehart L., K. "et al.". "J. Nat. Prod." 1988, "51", 1-21.] It is a strong antiviral agent against both DNA and RNA viruses like Herpes simplex virus type 1, a strong immunosuppressant that shows some potential in skin graft [Montgomery, D.; Zukoshi, C. F. "Transplantation" 1985, "40", 49.] and is also very cytotoxic. It shows strong activity against murine leukemia cells. Large amounts of Didemnin B were chemically synthesized and it was advanced to clinical trials by the National Cancer Institute. It has completed phase II human clinical trials against adenocarcinoma of the kidney [Taylor, S. A.; Goodman, P.; Stuckey, W. J. Stephens, R. L.; Gaynor, E. R. "Invest. New Drugs" 1992, "10", 55.] , advanced epithelial ovarian cancer [Cain, J. M.; Liu, P. Y.; Alberta, D.E.; Gallion, J.J.; Laufman, L.; O'Sullivan, J.; Weiss, G.; Bickers, J. N. "Invest. New Drugs" 1992, "10", 113.] , and metastatic breast cancer [Montgomery, D.; Zukoshi, C. F. "Transplantation" 1985, "40", 49.] . Unfortunately, the compound exhibited high toxicity through a high incidence of anaphylactic reactions in patients and trials were terminated [Nuijen, B.; Bouma, M.; Manada, C.; Jimeno, J.M.; Schellens, J. H. M.; Bult, A.; Beijnen, J. H. "Anti-Cancer Drugs" 2000, "11", 793.] .

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