Integrated approaches to discover and develop new therapeutic leads from marine cyanobacteria

Traditional approaches in natural products drug discovery have been highly effective in the discovery of clinically useful agents, accounting by some estimates for up to 70% of our approved drugs, either directly or by inspiring related agents to be chemically synthesized [1]. Nevertheless, the field continues to pioneer new advances in terms of approaches and classes of organisms under study, striving to maintain this record of success while at the same time introducing new innovations. At the present time, we have many highly sophisticated techniques available in analytical chemistry, molecular pharmacology, computational chemistry, synthetic organic chemistry, and chemical and molecular biology. Simultaneous integration of advances from these various fields is both challenging and highly enriching to natural products studies. The work of many students and researchers in my laboratory over the years, as well as our collaboration with numerous colleagues, have sought to innovatively explore the unique bioactive compounds of marine algae and cyanobacteria with the goal of identifying natural products of significance to biomedicine [2]. My presentation will describe several of the more recent and insightful of these projects that have utilized integrated approaches, including discovery and development of a novel anti-Chagas Disease agent, development of new MS and NMR algorithms to accelerate compound characterization, and biosynthesis of tertiary butyl groups in Nature. These multidisciplinary approaches have enriched the discovery process.

Acknowledgements: We thank the US National Institutes of Health for many years of support.

Keywords: marine cyanobacteria, molecular networks, drug discovery, biosynthesis.

References:

[1] Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 2016; 79: 629 – 661

[2] Kleigrewe K, Almaliti J, Tian IY, Kinnel RB, Korobeynikov A, Monroe EA, Duggan BM, Di Marzo V, Sherman DH, Dorrestein PC, Gerwick L, Gerwick WH. Combining mass spectrometric metabolic profiling with genomic analysis: A powerful approach for discovering natural products from cyanobacteria. J Nat Prod 2015; 78: 1671 – 1682