Nafisamycin, Cyclisation Product of a New Enediyne Precursor, Highly Cytotoxic Mansouramycins, Karamomycins Possessing a Novel Heterocyclic Skeleton and Further Unusual Secondary Metabolites from Terrestrial and Marine Bacteria.

Abstract

The search for new medically active compounds to overcome the countless diseases is one of the most relevant objectives worldwide. Medicinal plants were used previously in the traditional medicine and even now are important for the treatment of certain infections. However, the appearance of new diseases and new drug resistances stimulated the search for new sources of bioactive agents. The marine environment comprises nearly three quarters of the earth s surface, and can be considered as a soup of all imaginable types of microbes. Marine microorganisms, particularly bacteria, have provided new incentives for investigating marine natural products over the past 15 years, and also continue to be the subject of vigorous chemical investigation. This highlights their importance as a source of natural products. So, the search for new biologically active natural metabolites in bacteria may enable us to cure such drug resistances and unusual infectious diseases. In the present study, 10 terrestrial Streptomycetes and 15 marine-derived bacterial strains were selected on the bases of a chemical and biological screening. The isolates were scaled up under standard conditions, and the culture broths were usually extracted with ethyl acetate or passed through Amberlite XAD-columns, while the mycelial cake was extracted with ethyl acetate, followed by acetone. The crude extracts were purified using various chromatographic methods, including silica gel columns, Sephadex LH-20, PTLC and HPLC. The isolated compounds were dereplicated by means of AntiBase, the Dictionary of Natural Products (DNP) and the Chemical Abstracts. Structure elucidation occurred with the aid of spectroscopic techniques (MS, MS/MS, 2D NMR, etc.). In some cases, simple derivatives were synthesized. In general, all isolated compounds were investigated for various biological activities (e.g. as antimicrobial, anticancer agents, etc.). Twenty five bacterial strains were selected and subjected to culture optimization, working up and isolation of their metabolic constituents. From the extracts of these strains, 140 compounds were isolated, among them 61 new compounds, of which twelve had new skeletons. The remaining compounds were classified into 24 quinones, 22 macrolides, 6 peptides, 8 sulphur compounds, 4 chlorine containing metabolites, 2 polyenes and one enediyne derivative.