IB-96212, a novel cytotoxic macrolide produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation and biological activities.

A novel bioactive macrolide, IB-96212 has been isolated from the fermentation broth of a marine actinomycete, L-25-ES25-008. The strain belongs to the genus Micromonospora. The macrolide showed a very strong cytotoxic activity against P-388, and lower but significant activity against A-549, HT-29, and MEL-28 cell lines. We describe the isolation, taxonomy and fermentation of the producing strain as well as the isolation of IB-96212.

IB-96212, a novel cytotoxic macrolide produced by a marine Micromonospora. II. Physico-chemical properties and structure determination.

IB-96212, is a new member of spiroketal containing macrolide class of fermentation-derived natural products isolated from mycelial extracts of Micromonospora sp. The structure consists of a new aglycone which possesses a 26-membered macrolide ring system and of one deoxy sugar identified as L-rhodinose, this structure represents the first reported spiroketal macrolide natural product related to other macrolides, such as oligomycins, dunaimycins, citovaricin, rutamycin and ossamycin.

Two marine Agrobacterium producers of sesbanimide antibiotics.

Sesbanimides are cytotoxic compounds, originally isolated in 1983 from seeds of the leguminous plants Sesbania drummondii and Sesbania punicea. In this paper we describe the bacterial production of sesbanimides by two "marine Agrobacterium"; strain PH-103 which produces Sesbanimide-A and strain PH-A034C which produces Sesbanimide-C. The isolation and taxonomy of the producing microorganisms, fermentation and isolation of sesbanimides are reported.

Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activities.

A novel bioactive depsipeptide, thiocoraline, was isolated from the mycelial cake of a marine actinomycete strain L-13-ACM2-092. Based on morphological, cultural, physiological, and chemical characteristics, strain L-13-ACM2-092 was ascribed to the genus Micromonospora. Thiocoraline showed a potent cytotoxic activity against P-388, A-549 and MEL-28 cell lines, and also a strong antimicrobial activity against Gram-positive microorganisms. This compound binds to supercoiled DNA and inhibits RNA synthesis.

Thiocoraline, a novel depsipeptide with antitumor activity produced by a marine Micromonospora. II. Physico-chemical properties and structure determination.

Thiocoraline (1) is a new antitumor antibiotic isolated from the mycelium of Micromonospora sp. L-13-ACM2-092. Its structure was elucidated to be a novel cyclic thiodepsipeptide on the basis of spectroscopic methods.

Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein.

The effects of several members of the family of lamellarins, polyaromatic alkaloids isolated from tunicates belonging to the genus Didemnum, on the growth of several tumour cell lines and on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR), were investigated. Cytotoxicity experiments of lamellarins were performed on a panel of tumour cell lines, including two multidrug-resistant cell lines. Some lamellarins showed good anti-tumour activity, with similar levels of cytotoxicity against both the resistant and their corresponding parental cell lines. Two lamellarins displayed a high potency against lung carcinoma cells. Studies of the resistance modifier activity of the different lamellarins at non-toxic concentrations were also carried out in cells exhibiting MDR, and lamellarin I was selected for the highest chemosensitising activity. At non-toxic doses, verapamil and lamellarin I effectively increased the cytotoxicity of doxorubicin, vinblastine and daunorubicin in a concentration-dependent manner in multidrug-resistant cells, but the potency of lamellarin I as a MDR modulator was 9- to 16-fold higher than that of verapamil. In vitro measurements of rhodamine 123 accumulation in the multidrug-resistant Lo Vo/Dx cells suggest that lamellarin I reverses MDR by directly inhibiting the P-gp-mediated drug efflux. This work underscores the possibility of using these marine-derived compounds as a potential new source of anti-tumoral drugs active on resistant cells as well as of non-toxic modulators of the MDR phenotype.

A microtitre plate-based assay for the screening of beta-lactams.

A simple, rapid, sensitive and automatizable method for the detection and quantification of bacterial cell wall inhibitors has been developed. The procedure is characterized by the use of a micro-organism hypersensitive to beta-lactam antibiotics that contains an inducible cytosolic beta-galactosidase; this enzyme is released when the micro-organism cell wall is disrupted by the antibiotic action, and then measured by the use of a chromogenic substrate. The present method allows the detection of beta-lactam traces in other non-beta-lactam antibiotics, and has been successfully applied in the detection of small amounts of beta-lactams in biological fluids such as milk and Actinomycetes fermentation broths. The easy automatization of this method makes it specially suitable for the screening of new antibiotics of natural origin.