BRYOSTATIN & KAHALADIDE

MARINE BIODIVERSITY – ANTICANCER DRUG DEVELOPMENT

• Various active anticancer agents are derived from plants and terrestrial microbes.

• The oceans cover about 70% of the earth’s surface, and the marine environment includes tremendous biodiversity.

• The isolation of C-nucleosides from the Caribbean sponge, Cryptotheca crypta, four decades ago, provided the basis for the synthesis of cytarabine, the first marine derived anticancer agent to be developed for clinical use.

OCEANS – A HUB FOR BIODIVERSITY

STATUS OF MARINE RESEARCH

DRUG-LIKE MOLECULES IN PIPELINE

BRYOSTATIN

Bryostatin1 is currently in Oncology Clinical Phase II

• Bryostatin 1 is a macro cyclic natural lactone isolated from the marine bryozoan , Bugula neritina .

• It modulates the activity of protein kinase C (PKC), lacks tumor-promoting activity and shows differentiation inducing effects in various in vitro and in vivo models.

• It also has immunomodulatory properties, including the induction of cytokine release and expansion of tumor specific lymphocyte populations.

CHEMICAL STRUCTURE

KAHALADIDE FKahalalide F is currently in Oncology Clinical Phase II

• Kahalalide F (KF) is a cyclic peptide derived from the Hawaiian herbivorous marine species of mollusc , Elysia rufescens.

• Its diet is the green alga Bryopsis sp.• It shows antitumor activities both on

transformed cell lines and on tumor specimens derived from a variety of solid human tumors.

• The molecular basis of the tumoricidal activity of KF are not fully established.

The permeabilization of the plasma membrane leading to oncosis.

Alterations in lysosome morphology.

Inhibition of the ErbB3 signaling pathway.

CHEMICAL STRUCTURE

REFERENCES

• Gilberto Schwartsmann, Adriana Brondani da Rocha, Roberto GS Berlinck and Jose Jimeno Marine organisms as a source of new anticancer agents, THE LANCET Oncology Vol 2 April 2001.

• Dr. Fernando de la Calle Marine Genetic Resources: A Source of New Drugs, Biodiversity and Genetic Resources of the Deep Sea ITLOS, Hamburg. Sep, 29th 2007.

• Luis J. Cruz, Juan R. Luque-Ortega, Luis Rivas and Fernando Albericio Kahalalide F, an Antitumor Depsipeptide in Clinical Trials, and Its Analogues as Effective Antileishmanial agents, Molecular pharmaceutics, Revised Manuscript Received March 7, 2009; Accepted March 24, 2009.

”In one drop of water are found all thesecrets of the oceans”