Recent studies have demonstrated that marine bacteria, likely their terrestrial counterparts, may be a prolific source of unique compounds. To date, even though both shallow water and deep marine habitats have been shown to contain a taxonomically diverse array of microorganisms, the investigation of these microorganisms has largely been ignored by natural products chemists. Marine bacteria have the potential to provide a virtually untapped source of new chemotherapeutic agents. The goal of the proposed research project is the discovery of new antineoplastic agents from bacteria isolated from the marine environment. Bacteria will be isolated from both shallow and deep ocean sediments, as well as shallow sea water. To maximize the detection of pharmaceutically relevant compounds, extracts of liquid bacterial cultures will initially be assayed for biological activity using antimicrobial, antiviral, DNA-binding , and solid tumor cytotoxicity assays. Those culture whose extracts exhibit promising activity will be scaled-up to obtain extracts for the isolation and structure identification of the active compounds. The chemical structures of the biologically active secondary metabolites will be deduced through both chemical and spectroscopic methods, and, in particular, through the application of new and unique one- and two-dimensional NMR techniques.Purified cytotoxic compounds will then be subjected to further analysis to gain insight into the mechanism of action, and whether the cytotoxicity of a given compound is the result of inhibition of topoisomerase II.
| Schumacher, R W; Davidson, B S; Montenegro, D A et al. (1995) Gamma-indomycinone, a new pluramycin metabolite from a deep-sea derived actinomycete. J Nat Prod 58:613-7 |
