This Small Business Innovation Research Phase I project seeks to develop new anticancer drug leads from secondary metabolites of thermophilic cyanobacteria, a new industrial resource. The Phase I research will isolate, assay, and characterize the novel anti-tumor metabolites that the applicant has already detected in crude extracts and enriched fractions of several cultured strains. The profile of activities of those extracts in the NCI 60-cell line cancer screens was unprecedented. Further fractionation for chemical purification will follow bioactivity-directed protocols. Purified antitumor compounds that are novel in structure or mechanism of activity will undergo in vitro screens: tumor cell screens as well as recently developed, cell-based, anticancer mechanism screens at the University of Utah, and 60-cell line tumor cell panel screens at the NCI. During the Phase I funding period, culture optimization for cell and metabolite yields will begin with flask cultures and will scale up to 15-L thermophile photobioreactors designed by the applicant. Phase II tasks will include further chemical characterization of the antitumor metabolite(s), attempted chemical synthesis, and optimization of larger-scale culture scale-up technologies for thermophilic cyanobacteria. Promising leads will be out-licensed to, or co-developed with a pharmaceutical company.
