Bryostatin

Bryostatins are a group of macrocyclic lactones first discovered in the late 1960s in a species of bryozoan, Bugula neritina. It is believed to be produced by symbiont bacteria to protect the bryozoan larva from predation, they have cytotoxic properties and are under investigation as anti-cancer agents and as a memory enhancement agent. Bryostatin has been shown to be a potent activator of protein kinase C.

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In vitro trials have shown bryostatins to act synergistically with other anti-cancer drugs and to modulate protein kinase C (PKC) activity, with a potent antileukemic effect and action against lung, prostate and non-Hodgkin's lymphoma tumor cells. Human clinical trials have been less promising, but suggest bryostatins to have a potentially useful synergistic action with other chemotherapeutic agents.

Bryostatin has appeared very promising enhancing memory in animal models. Bryostatin was able to increase the duration of memory retention of the marine slug Hermissenda Crassicornis by over 500% ^[1], and was able to dramatically increase the rate of learning in rats^[2]. It has been rumored that it is now being investigated in human testing, possibly for treatment of Alzheimer's disease. Bryostatin is thought to potentiate memory by activating PKC.

The low concentration in bryozoans (to extract one gram of bryostatin, roughly one tonne of the raw bryozoans is needed) makes extraction unviable for large scale production. Due to the structural complexity, synthesis has proved difficult, with only a few total syntheses reported so far. However, structurally simpler synthetic analogs have been prepared which exhibit similar biological profile and in some cases greater potency, which may provide a practical supply for clinical use. ^[3]

External links

• Drugs from the seas – current status and microbiological implications, Proksch P, Edrada RA, Ebel R, Appl Microbiol Biotechnol. 2002 Jul;59(2-3):125-34.
• Bryostatin 1 Aphios report
• Bryostatins 1-3 QXHealth summary

1. ^  "Bryostatin enhancement of memory in Hermissenda." Kuzirian AM, Epstein HT, Gagliardi CJ, Nelson TJ, Sakakibara M, Taylor C, Scioletti AB, Alkon DL. Biological Buleitin, 2006 Jun;210(3):201-14.
2. ^  "Dual effects of bryostatin-1 on spatial memory and depression." Sun MK, Alkon DL. European Journal of Pharmocology, 2005 Apr 4;512(1):43-51.
3. ^  "The Practical Synthesis of a Novel and Highly Potent Analogue of Bryostatin." P. A. Wender, J. L. Baryza, C. E. Bennett, F. C. Bi, S. E. Brenner, M. O. Clarke, J. C. Horan, C. Kan, E. Lacote, B. Lippa, P. G. Nell, T. M. Turner, Journal of the American Chemical Society, 2002, vol. 124, pp. 13648-13649.