Lavendomycin, a new basic peptide antibiotic containing novel amino acids, has been isolated from the culture broth of a streptomyces designated as Streptomyces lavendulae subsp. brasilicus. The antibiotic obtained as colorless crystals (C₂₉H₅₀N₁₀O₈, MW 666) is active against Gram-positive bacteria in vitro and in vivo, however, inactive against Gramnegative bacteria and fungi. An acute toxicity of the antibiotic in mice was LD₅₀>2 g/kg by subcutaneous injection.

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A new antibiotic, trienomycin A, has been isolated from the culture broth of Streptomyces sp. No. 83-16. The physico-chemical characteristics of the antibiotic suggested that it belongs to the group of ansamycin antibiotics with a triene moiety in the molecule. The molecular formula of trienomycin A is C₃₆H₅₀N₃O₇( MW 622). The antibiotic possesses potent cytocidal activity against HeLa S₃ and PLC hepatoma cells at concentrations of 0.1 and 0.01 μg/ml (IC₅₀ value) respectively. However, trienomycin A showed no antimicrobial activity against the bacteria, fungi and yeasts examined with the exception of weak activity versus Piricularia oryzae at a concentration of 1, 000 μg/ml.

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Plastatin and the known fungal metabolite, luteosporin, have been isolated from fermentations of Penicillium chermesinum as inhibitors of porcine pancreatic phospholipase A₂ (PLA₂). Structure 1 for plastatin was deduced from its spectroscopic properties. Plastatin and luteosporin inhibited pancreatic PLA₂ competitively with Ki values of 0.89 μM and 12.8 μM, respectively. PLA₂ preparations from Naja naja and Crotalus adamanteus were not significantly inhibited by plastatin and luteosporin.

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A series of glycopeptide antibiotics related to the vancomycin-ristocetin family have been successfully analyzed by fast atom bombardment mass spectrometry (FABMS). The FAB mass spectra of glycopeptides weighing up to 2, 100 daltons exhibit intense molecular ions and fragment ions from which information concerning carbohydrate composition and sequence are readily obtained. Careful adjustment of the FABMS experimental conditions has enabled the accurate masses of the glycopeptides to be determined by high resolution FABMS with an accuracy of better than six ppm. Comparison of the observed molecular ion cluster pattern with calculated isotope distributions reveals the precise number of chlorine atoms in these molecules, which, together with the accurate mass data, can be used to restrict the number of possible elemental compositions to a meaningfully small value. These techniques have been used to characterize several glycopeptides of known structure including ristocetin, actinoidin, avoparcin, vancomycin and A35512B, as well as aridicins A, B and C which are three new, novel members of the vancomycin class.

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The influence on the antibacterial activity of introducing a 6α-methoxy group into carbenicillin, and various 6α-substituents into sulbenicillin and piperacillin was examined. Further variations of the side chain aryl group were examined in the 6α-methoxy substituted series. This led to the identification of disodium 6β-(D, L-2-carboxy-2-thien-3-ylacetamido)-6α-methoxypenicillanate (5b) as a β-lactamase stable derivative with useful activity against Enterobacteriaceae, and disodium 6β-[D-2-(4-aminophenyl)-2-sulfoacetamido]-6α-methoxypenicillanate (6e) with slightly lower activity against the Enterobacteriaceae but more active against Pseudontonas aeruginosa.

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The synthesis of a series of 7R-[(R)-2-[3-[5-pyrimidinyl]ureido]-2-(aryl)acetamido]-3-cephem-4-carboxylates is described. Variation of the substituents at the 3-position in the cephem nucleus, at the 2-position of the pyrimidine ring, and of the phenyl residue in the acyl side chain is carried out. Qualitative structure-activity relationships in this series are discussed. VX-VD 2, the most interesting compound, exhibits broad antimicrobial activity against Gram-negative bacteria, including Pseudomonas aeruginosa.

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This report defines the transformations that antitumor antibiotic CC-1065 underwent under basic and acidic conditions. The isolation, purification, characterization, and biological properties of a cyclopropapyrroloindole fragment, and an acidic fragment, PDE-I dimer, from a mild alkaline fragmentation and the phenolic product, AAP, resulting from alkylation of acetic acid by the cyclopropyl function are described.

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Radical formation during autooxidation of the polyene antibiotic amphotericin B was monitored by following the kinetics of decay of the ESR signal of a stable nitroxide. The kinetics were seen to depend both on antibiotic and on nitroxide concentration. The radicals formed were studied by spin trapping. Three preparations-clinical Fungizone, amphotericin B suspended in buffer, and amphotericin B in buffer-10% dimethyl sulfoxide-yielded spin adducts of different nature and/or concentrations. In the absence of dimethyl sulfoxide, amphotericin B yielded at least two carbon-centered radicals whose spectra indicated restricted mobility. This suggests that the radicals arise from the whole amphotericin B molecule located in molecular aggregates present in the preparations, and not from smaller and possibly more water-soluble fragments of the antibiotic. In the presence of dimethyl sulfoxide the spin adducts derived from secondary carbon radicals originated from this solvent. Their spectra were indicative of fast tumbling. Direct evidence for autooxidation was obtained by measuring oxygen consumption. All processes examined occurred at the same time scale observed for drug inactivation, in agreement with the idea that loss of activity is due to antibiotic autooxidation.

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A method is described by which the growth inhibitory effects of cytotoxic compounds and fermentation broth cultures on adherent tumor cell lines can be quantitated. Cells are seeded into 96-well microtiter plates and 16 hours later the test compounds or broths are added to the wells. Cell growth is measured after three days (B16 mouse melanoma cells) or six days (HT-29, human colon carcinoma cells) by first fixing adherent cells, staining with Giemsa stain, washing away excess stain, then solubilizing stained cells with HCl. Absorbance is determined using a microELISA spectrophotometer and the data are transferred to and analyzed by a computer. The assay is rapid and reproducible and can be used to identify fermentation broths with cytotoxic components. Addition of DNA into the assay mixture (cells plus compound) inhibits the cytotoxic activities of certain DNA-reactive agents. The results of this study demonstrate the application of this assay system for primary and secondary evaluation of fermentation broths for in vitro antitumor activity.

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Safracins A and B, new antibiotics produced by Pseudomonas fluorescens A2-2, were tested for antitumor activity against mouse tumors . Structurally, these antibiotics belong to the saframycin family of antibiotics, and safracin B is 21-hydroxysafracin A. They showed antitumor activity against L1210 and P388 leukemias and B16 melanoma . The toxic and effective doses of safracin B were much lower than those of safracin A. Safracin B also prolonged the life span of tumor-bearing mice to a greater extent than safracin A. These results indicate that the α-carbinolamine structure plays an important role in the antitumor action of this type of antibiotic. Both safracins were, however, ineffective when their administration route differed from that used for inoculating tumor cells.

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The following aminopeptidase (AP) activities were found to be associated with the surface of mouse spleen cells: Leu-AP (138 pmol/10⁵ cells×minute) and AP-B (16 pmol/10⁵ cells×minute with Lys-β-naphthylamide as substrate and 21 pmol/10⁵ cells×minute with Arg-β-naphthylamide substrate); AP-A activity was not detected by the assay system applied. The immunoactive peptide bestatin inhibited the Leu-AP, while AP-B activity decreased in the presence of both arphamenines A and B and bestatin. No effects on these enzymes were caused by amastatin (an AP-A inhibitor), FK-156, FK-565 and Bu-2743E; the latter peptide turned out to be not an inhibitor of cell surface associated microsomal Leu-AP but an inhibitor of cytosolic Leu-AP. The immunoactive peptides bestatin, arphamenines A and B, and amastatin increased [³H]thymidine incorporation into spleen cells containing lymphocytes and macrophages. These mitogenic actions were not observed when macrophages were removed from the cultures or the cells had been stimulated with ConA or LPS. The lactoyl- and heptanoyl peptides FK-156 and FK-565 caused a mitogenic action on lymphocytes independently of the presence of macrophages. The inhibitor of cytosolic Leu-AP did not change the incorporation into lymphocytes.

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FCE 22250 (3-(N-piperidinomethylazino)methylrifamycin SV) is a member of the new class of 3-azinomethylrifamycins characterized by a long persistance in animals, a good oral absorption and a broad antibacterial spectrum including mycobacteria. In the experimental mice infection sustained by Mycobacterium tuberculosis H37Rv, FCE 22250 shows an efficacy 14 times higher than rifampicin and is still therapeutic when administered once every three weeks.

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A gene that complements argG mutations was cloned from Streptomyces coelicolor and Streptomyces lividans by using pIJ702 as a vector. The recombinant plasmid pMCP25 complemented argG mutations of S. lividans and S. coelicolor. The inserted DNA of pMCP25 was able to hybridize with argG⁺ strains of S. lividans, S. coelicolor, S. lavendulae and S. alboniger but not with argG mutants of these strains.

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