The bark extracts of Annona squamosa yielded a new bioactive acetogenin, squamotacin (1), and the known compound, molvizarin (2), which is new to this species. Compound 1 is identical to the potent acetogenin, bullatacin (3), except that the adjacent bistetrahydrofuran (THF) rings and their flanking hydroxyls are shifted two carbons toward the gamma-lactone ring. Compound 1 showed cytotoxic selectively for the human prostate tumor cell line (PC-3), with a potency of over 100 million times that of Adriamycin.

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Two new xanthone antibiotics, citreamicin delta (1) and epsilon (2), with potent activity against Gram-positive pathogens including multidrug-resistant Staphylococcus aureus (MDRSA) were discovered. Compounds 1 and 2 exhibited MIC values < 1 microg/mL versus a number of resistant strains. The compounds were obtained from EtOAc extracts of Streptomyces vinaceus and were purified by countercurrent chromatography and reversed-phase HPLC. Their structures were elucidated using primarily NMR and mass spectroscopy.

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Resistance to currently available antibiotics has become a widely recognized crisis in the medical community. To address this, many companies and researchers are refocusing their attention towards natural products, which have an excellent track record of producing effective antibacterial drugs. The AMRI natural product library was screened for activity against multi-drug resistant Staphylococcus aureus (MDRSA). The active samples were counter screened for cytotoxicity against the human hepatocellular carcinoma HepG2 cell line to determine an in vitro therapeutic index (in vitro TI). Those samples with a high in vitro TI were selected for fractionation and dereplication. This led to the discovery of a new anthracycline structure. This metabolite, named mutactimycin E (1), exhibited moderate activity against several gram positive organisms. Here we report the isolation, structure elucidation and biological activities of this new compound. Keywords mutactimycin, anthracycline, antibiotic, AmycolatopsisIt has been known for some time that resistance to existing antibiotics is increasing. This is particularly true in hospital settings, but is also found in community-acquired infections. This development, when coupled with the decision by many pharmaceutical companies to abandon antibacterial research in the 1980's and 1990's, resulted in the absence of new antibiotics to combat current resistance mechanisms. In an effort to address this urgent need, we began a screening campaign to identify novel antibiotics from our natural product library. Natural products, particularly those produced by microbial fermentation, were the direct source or inspiration for almost all antibiotics used today and remain the richest source for new antibacterial compound series. Our extensive library consisting of over 280,000 samples was screened for activity against a multi-drug resistant strain of Staphylococcus aureus (ATCC 43300). The hits arising out of this assay were then tested against the human hepatocellular carcinoma cell line HepG2 to filter out those samples where activity was the result of general cytotoxicity. The resulting subset of samples possessing selectivity for the bacterial target were then fractionated on an HPLC system employing UV, evaporative light scattering, and MS detectors. The eluted fractions were collected into 96-well microtiter plates and submitted for bioassay. Active compounds were subsequently dereplicated on the basis of MS and UV data.One of the hits resulting from our efforts originated from the EtOAc extract of Amycolatopsis strain 17128. A scaledup fermentation of the active strain and subsequent purification of the active compound by reverse phase HPLC yielded mutactimycin E (1) as an orange solid (Fig. 1). LC/MS data for 1 indicated a molecular weight of 560 Daltons. This piece of information along with the UV spectrum was used to search internal and external databases [1]. Analysis of the hits from this search indicated

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