Enzyme Inhibitory metabolites from marine micro-organisms

PUNGITORE, CARLOS RODOLFO; LAATSCH, HARMUT

Oldenburg, Alemania

Congreso; Netzwerktagung Alexander von Humboldt; 2009

Alexander von Humboldt Foundation

More than 70% of our planet?s surface is covered by oceans, and life on Earth has its origin in the sea. Many marine organisms are soft bodied and have a sedentary life style necessitating chemical means of defense. Therefore, they have evolved the ability to synthesize toxic compounds or to obtain them from marine microorganisms. Taking into account this situation, it is clear that a more systematic, eco-driven study of natural product synthesis by marine organisms is necessary. In recent years, marine natural product bioprospecting has yielded a considerable number of drug candidates, with some drugs such as, the cephalosporins, cytarabine and vidarabine, already well established on the market, the granting of Orphan Drugstatus to bryostatin-1, squalamine and ET743 in the past 2 years, and more than a dozen further marine compounds or derivatives currently in clinical trials. We intend to focus our search in looking for inhibitory activity of enzymes, such as DNA polymerases, Topoisomerases and Reverse Transcriptase. DNA Polymerases and Topoisomerases are enzymes that play a crucial role in DNA metabolism events such as replication, transcription and recombination. Several DNA polymerase and topoisomerase inhibitors have been introduced into clinical trials as potent anticancer drugs, however, more potent and specific agents are still needed. Reverse Transcriptase, despite their longstanding use in the context of highly active anti-retroviral therapy (HAART)