Balhimycin, a new glycopeptide antibiotic produced by Amycolatopsis sp. Y-86,21022. Taxonomy, production, isolation and biological activity.

A new glycopeptide antibiotic, balhimycin, has been isolated from the fermentation broth of a Amycolatopsis sp. Y-86,21022. Balhimycin belongs to the vancomycin class of glycopeptides and contains a dehydrovancosamine sugar. The biological activity of balhimycin has been compared extensively with that of vancomycin against methicillin resistant staphylococci and also against anaerobes. Balhimycin is marginally superior to vancomycin in its in vitro activity against anaerobes and in its bactericidal properties.

Aranorosinol A and aranorosinol B, two new metabolites from Pseudoarachniotus roseus: production, isolation, structure elucidation and biological properties.

Two new secondary metabolites, aranorosinol A (1) and aranorosinol B (2), were isolated from a strain of Pseudoarachniotus roseus. Their structures were elucidated on the basis of their spectral properties and chemical transformations and were found to be similar to aranorosin (3) isolated from the same strain.

Mersacidin, a new antibiotic from Bacillus. In vitro and in vivo antibacterial activity.

Mersacidin is a new peptide antibiotic of the proposed lantibiotic family. It is active in vitro and in vivo against Gram-positive bacteria including the methicillin-resistant Staphylococci. Its in vitro activity is less than those of vancomycin and erythromycin but it shows much higher activity in the in vivo system than can be expected from the in vitro testing results. A water soluble potassium salt has been prepared which has an activity profile similar to that of mersacidin, but has better in vivo activity against Streptococcus pyogenes than the parent compound.

Deoxymulundocandin--a new echinocandin type antifungal antibiotic.

A new echinocandin type antifungal antibiotic, deoxymulundocandin, C48H77N7O15, was isolated from the culture filtrate and mycelia of a fungal culture, Aspergillus sydowii (Bainier and Sartory) Thom and Church var. nov. mulundensis Roy (Culture No. Y-30462). The structure was established by comparative GC-MS analyses of the derivatized acid hydrolysates of deoxymulundocandin and mulundocandin as well as by the high field NMR experiments (COSY, NOESY and DEPT).

Alisamycin, a new antibiotic of the manumycin group. I. Taxonomy, production, isolation and biological activity.

Alisamycin is a new member of the manumycin group of antibiotics produced by Streptomyces sp. HIL Y-88,31582, which taxonomically appears to be Streptomyces actuosus. Alisamycin is active against Gram-positive bacteria and fungi, and has a weak antitumour activity.

Butalactin, a new butanolide antibiotic. Taxonomy, fermentation, isolation and biological activity.

Butalactin, [2-(4',5'-epoxy-hex-2'(E)-en)oyl-2-hydroxy-3-hydroxymethyl-2, 3-(Z)-butanolide] is a new antibiotic produced by Streptomyces sp. HIL Y-86,36923. Taxonomically, the producing organism most closely resembles Streptomyces corchorusii. The strain also produces cineromycin B. Though butalactin is structurally related to 'signal molecules' such as A-factor, the anthracycline inducing factors and the virginiae butanolides, it does not show inducing activity for antibiotic production or aerial mycelium formation in the indicator strain. Butalactin possesses a weak antibiotic activity against Gram-positive and Gram-negative bacteria.

Immunomodulation by the new synthetic thiazole derivative tiprotimod. 2nd communication: immunopharmacological activity.

The thiazole derivative [2-(3-carboxy-1-propylthio)-4-methyl-1,3-thiazole] acetic acid (tiprotimod, HBW 538) a new synthetic immunopotentiator of low molecular weight, has been tested in vivo and ex vivo in various experimental models. Its influence on parameters of macrophage functions, on DTH (delayed type hypersensitivity)-reaction and antibodies to sheep erythrocytes (SRBC), Tetanus toxoid and heatkilled E. coli bacteria in mice, and in the popliteal lymph node assay in rats was investigated. When mice were treated with the test substance i.v., i.p., or p.o. in a dose range from 1-100 mg/kg, a time and dose-dependent stimulation of macrophage activity was observed. The drug was able to enhance the DTH-response against SRBC and to stimulate the humoral immune response against Tetanus toxoid and heat-killed E. coli. In the popliteal lymph node assay, a murine graft-vs-host model, a stimulating effect of the substance was observed when it was administered at the same time of the grafts to rats. These results demonstrate that tiprotimod is a potent immunopotentiator for both humoral and cell mediated immune response in experimental animals.

Immunomodulation by the new synthetic thiazole derivative tiprotimod. 1st communication: synthesis and structure-activity relationships.

A series of carboxyalkylthio-substituted thiazole-carboxylic acids was synthesized and examined for macrophage activation and stimulation of the DTH (delayed type of hypersensitivity)-reaction. The structure-activity relationship in this series of new immunomodulators is discussed. Broadest immunological activity was seen for [2-(3-carboxy-1-propylthio)-4-methyl-1,3-thiazole]acetic acid (tiprotimod, HBW 538) which was selected for further studies.

Synthesis and structure-activity relationships in the cefpirome series. I. 7-[2-(2-Aminothiazol-4-yl)-2-(Z)-oxyiminoacetamido]-3-[(su bstituted-1-pyridinio)methyl]ceph-3-em-4-carboxylate s.

7-[2-(2-Aminothiazol-4-yl)-2-(Z)-oxyiminoacetamido]-3-[(s ubs tituted-1-pyridinio)methyl]ceph-3-em-4-carboxylates II are a group of beta-lactam antibiotics with extraordinary high antibacterial activity. The promising member of this group, cefpirome (HR 810, II-1) is a candidate for clinical use. Synthetic pathways to II starting from cefotaxime derivatives I or 7-aminocephalosporanic acid (7-ACA) are described. A preferred method for the conversion of I to II or 7-ACA to precursors III respectively employs iodotrimethylsilane and an excess of the pyridine base. Structure-activity studies reveal an optimum overall activity in the series of pyridines with fused saturated and unsaturated rings or cyclopropyl- and alkoxy substituents. Favorable oxyimino substituents are methyl, ethyl, difluoromethyl and carbamoylmethyl groups. Acidic substituents lead to decreased activity against Staphylococcus aureus SG 511. Introduction of halogen in the thiazole nucleus causes improvement of activity against the K1 beta-lactamase producing Klebsiella aerogenes 1082 E strain.

Synthesis and structure-activity relationships in the cefpirome series. II. Analogues of cefpirome with different 7-heteroarylacetamido and 3'-ammonium substituents.

The synthesis and antibacterial activity in vitro of 7-(2-heteroarylacetamido)-3-[(2,3- cyclopentenopyridinium)methyl]cephalosporins and of some related compounds with different ammonium functions in 3'-position are described. The 7-[5-amino-1,2,4-thiadiazol-3-yl] and the 7-[4-aminopyrimidin-2-yl] analogues of cefpirome and compounds with 3-aliphatic ammoniummethyl functions have excellent antibacterial activity. Cephalosporins with different N-heterocycles other than pyridine in 3'-position are less active than their 3-pyridiniummethyl analogues. Attachment of a pyridinium group to a cephem at C-3 via a thiomethyl or an aminomethyl bridge causes reduction of antibacterial activity.

Cefodizime, an aminothiazolylcephalosporin. V. Synthesis and structure-activity relationships in the cefodizime series.

The synthesis as well as in vitro antibacterial activity and pharmacokinetic behavior of cefodizime (HR 221, 1a), its analogs and derivatives is described. In this comparison, cefodizime stands out for its balance between its high antibacterial activity, prolonged elimination half-life and high AUC in mice and dogs.

HR 810, a new parenteral cephalosporin with a broad antibacterial spectrum.

3-[(2,3-Cyclopenteno-1-pyridinium)-methyl]-7-[2-syn-methoximino-2-(2-aminothiazol-4-yl)-acetamido]-ceph-3-em-4-carboxylate (HR 810) is a new cephalosporin derivative with an extremely broad antimicrobial spectrum. It is active against all bacterial species of clinical relevance, including strains which are frequently resistant towards cephalosporins of the third generation.