Differences in ion-channel formation by ampullosporins B, C, D and semisynthetic desacetyltryptophanyl ampullosporin A.

Peptaibol-type ampullosporins B (2) and D (4) are capable of forming ion-conducting pores in planar lipid bilayer membrane prepared from soybean phosphatidylcholine in a similar manner as it was shown for ampullosporin A (1). However, the isomeric ampullosporin C (3) was required in 20-fold higher concentration to afford a comparable effect. In contrast to 1, 2, 3 and 4, the desacetyltryptophanyl ampullosporin A (5) failed to form ion channels. The results suggest that the sequence of amino acids especially at positions 8-10, the nitrogen-terminal acetyl residues and tryptophane are major factors determining ion-channel formation within bilayer membranes. The differences in membrane activities were comparable to the observed biological activities.

Differentiation between inducers of apoptosis and nonspecific cytotoxic drugs by means of cell analyzer and immunoassay.

Differentiation between specific and nonspecific cytotoxic drugs by means of cell analyzer and immunoassay is described. The determination of antiproliferative, cytotoxic, and apoptotic effects as well as enlargement of cells in response to toxic compounds can be used for the disclosure of compounds with a specific mode of action. The usefulness of the procedure was demonstrated with camptothecin (1) as a cytotoxic drug and established inducer of apoptosis. Aphidicolin (2) and the new compound oxoaphidicolin (3) were shown to display no comparable effect. Isolation and structural data of 3 are reported.

[Rugulosuvines A and B--diketopiperazine alkaloids from Penicillium rugulosum and Penicillium piscarium fungi]. / Rugulozuviny A i B--diketopiperazinovye alkaloidy gribov Penicillium rugulosum i Penicillium piscarium.

Two diketopiperazine alkaloids, rugulosuvines A and B (tryptophan and phenylalanine are precursors), were isolated and purified from the culture liquid of Penicillium rugulosum VKM F-352 and Penicillium piscarium VKM F-325 fungi. Physical and physicochemical studies showed the absolute structure of rugulosuvine A. The absolute structure of rugulosuvine B was demonstrated to be similar to that of rugulosuvine A.

Disclosure of new and recurrent microbial metabolites by mass spectrometric methods.

The application of modern mass spectrometry methods (SI-CID-MS/MS; MSn) in the disclosure of new and recurrent microbial metabolites is discussed. Spray ion (SI) sources coupled to different kinds of mass analyzers enable the determination of molecular weights and chemical formulas of given samples even in mixtures. Diagnostic fragment formation by collision-induced dissociation (CID-MS/MS) and MSn experiments using ion trap mass analyzers are shown as another indispensable source of structural information. Due to the development of benchtop-type mass spectrometers coupled to high-performance liquid chromatography (HPLC), MS can be practised in almost every laboratory as a powerful tool in natural product analysis. Examples are given for special MS applications in identification of bioactive metabolites from screening strains.

New diketopiperazine alkaloids from Penicillium fellutanum.

Four new diketopiperazine alkaloids (1-4) were isolated from cultures of Penicillium fellutanum, and their structures were determined by MS and NMR measurements.

New macrodiolide antibiotics, 11-O-monomethyl- and 11, 11'-O-dimethylelaiophylins, from Streptomyces sp. HKI-0113 and HKI-0114.

Elaiophylin (1) and two new methyl derivatives, 11-O-monomethylelaiophylin (2) and 11,11'-O-dimethylelaiophylin (3), were isolated from the mycelium cake of Streptomyces strains HKI-0113 and HKI-0114. The structures of 2 and 3 were determined by mass spectrometric and NMR investigations. Compounds 2 and 3 display antimicrobial and moderate cytotoxic activities.

Demethyl mutactimycins, new anthracycline antibiotics from Nocardia and Streptomyces strains.

New anthracycline antibiotics 3'-O-demethyl mutactimycin (3) and 4-O,3'-O-didemethyl mutactimycin (4) were isolated from two actinomycetes strains, Nocardia transvalensis and Streptomyces sp. GW 60/1571. The chemical structures were elucidated by mass spectrometry and NMR spectroscopy. Antibiotic 3 displayed moderate antimicrobial activity against Gram-positive bacteria and cytotoxicity against P388, L1210 and HeLa tumor cells (IC50; 9.6, >25 and 20 microg/ml, respectively).

Nocardicyclins A and B: new anthracycline antibiotics produced by Nocardia pseudobrasiliensis.

Nocardicyclins A (1) and B (2), new anthracycline antibiotics have been isolated from the mycelial cake of Nocardia pseudobrasiliensis IFM 0624 (JCM 9894). The molecular formulae of 1 and 2 have been determined as C30H35NO11 and C32H37NO12, respectively, and the structures were characterized by 1- and 8-methoxyl groups, a 10-carbonyl group and a novel carbon-methylated aminosugar constituent. Nocardicyclin A (1) exerts cytotoxic activity against L1210 and P388 leukemia. Nocardicyclins A (1) and B (2) are active against Gram-positive bacteria including Mycobacterium spp. and Nocardia spp., but inactive against Gram-negative bacteria.

Ampullosporin, a new peptaibol-type antibiotic from Sepedonium ampullosporum HKI-0053 with neuroleptic activity in mice.

Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.