Enniatins produced by Fusarium dimerum, an endophytic fungal strain.

Cyclohexadepsipetides enniatin B, B1 and G were isolated from the cultivation broth of Fusarium dimerum Penzig, an endophyte of Magnolia x soulangeana. Their production was about 350 mg l(-1) after 96 h of submerged cultivation in Sabouraud maltose medium. Isolated enniatins inhibited growth of selected microorganisms and activity of 12-lipoxygenase with IC50 = 0.73 mg l(-1).

Biosynthesis and biological activity of enniatins.

Enniatins are N-methylated cyclohexadepsipeptides (CHDPs), composed of three units each of N-methylated branched-chain L-amino acid and D-2-hydroxy acid arranged in an alternate fashion. These low-molecular secondary metabolites are produced by Fusarium species, typical mycotoxin producing fungi. Enniatins are known for their ionophoric, phytotoxic and anthelmintic effect, antibiotic activity and recently their potent cytotoxic activity against cancer cell lines was shown. They act also as inhibitors of drug efflux pumps. Biosynthesis, biological activity, and the structural characteristics of these microbial metabolites were summarized in this review.

Identification of the configuration of neosartorin by long-range nuclear Overhauser effect measurements.

The relative configuration of the two xanthene units of neosartorin, a new ergochrome biosynthesised by the soil mould Neosartorya fischeri, was determined using a 1D double-pulsed field gradient spin-echo NOESY experiment. It was found that both units have the same relative stereochemistry. Long-range nonbonding interactions between the substituents of different xanthene units stabilise the nonplanar configuration of the two aromatic rings A and A' connecting both monomer units of neosartorin.

OR-1--a mixture of esters of glyceric acid produced by Penicillium funiculosum and its antitrypsin activity.

A mixture of related metabolites (denoted OR-1) was isolated from the fermentation broth of Penicillium funiculosum together with mitorubrinic acid. Structurally OR-1 is glyceric acid esterified with C14-C18 fatty acids. Steady-state studies revealed that OR-1 behaved like an uncompetitive trypsin inhibitor with Ki 17.6 mumol/L.

Vermiculine: a diolide with immunoregulatory activity.

Vermiculine (1), is a macrodiolide which displays a selective effect on certain reactions of cellular immunity. This paper summarizes data on its biological activity, isolation, microbial production, chemical properties and methods for its synthesis.

[Macrodiolides--chemical properties and activity in a biological model]. / Makrodiolidy--chemické vlastnosti a úcinky na biologické modely.

Diolides, often classified into a group of macrolides, represent a heterogenous group of microbial metabolites whose common feature is the presence of a cyclic diester moiety in their structure. These compounds have cytotoxic, antiviral, anthelmintic or immunosuppressive activities and they were effective agents against some autoimmune diseases. Diolides, contrary to macrolides, showed a substantially lower antibacterial activity. The current data on the chemical properties and biological activity of diolides are presented in this paper.

[Evaluation of the quality of mexiletine hydrochloride using capillary electrophoreses]. / Hodnotenie kvality hydrochloridu mexiletínu kapilárnou elektroforézou.

Mexiletine hydrochloride and its potential impurity xylenol were determined by micellar electrokinetic chromatography in a 25 cm long capillary. The effect of parameters--temperature, electric field, concentration of analyzed compounds, type and composition of background electrolyte--on the separation of analytes and precision of analysis was studied. The advantage of the elaborated method is a very short time of analysis (2.3 min) at the sufficient level of precision and reliability of results.

[Preparation and antineoplastic activity of acylhydrazones of R- and S-usnic acid]. / Príprava a protinádorové úcinky acylhydrazónov R- a S-usnovej kyseliny.

Hydrazones of R- and S-usnic acid were prepared by condensation of the appropriate enantiomer of usnic acid with hydrazides of aromatic acids. Prepared compounds were characterized by spectral methods. Reaction kinetic was studied with capillary electrokinetic chromatography, enantiomeric purity of products was checked by capillary electrophoresis in the presence of gamma-cyclodextrin. Obtained hydrazones were tested as prospective antimitotic agents. The antitumor activity was screened in vitro on human tumor cell lines. The overall activity of tested compounds was low, however, the R- enantiomers were more active than their opposite stereoisomers.

Separation of morphine and its oxidation products by capillary zone electrophoresis.

Separation of morphine and its oxidation products (10-S-hydroxymorphine, pseudomorphine and morphine N-oxide) by capillary zone electrophoresis in Tris-borate buffer in the presence of cyclodextrins was studied. Pyridoxine was used as an internal standard.

Production of (-)-mitorubrinic acid byPenicillium vermiculatum.

Biosynthesis of (-)-mitorubrinic acid and (-)-vermistatin byPenicillium vermiculatum strain IV/5 was stimulated by high concentration of glucose and urea as a C and N source, respectively. Effect of phosphate, trace elements and organic acids was also studied.

Depsides and depsidones as inhibitors of HIV-1 integrase: discovery of novel inhibitors through 3D database searching.

Seventeen lichen acids comprising despides, depsidones, and their synthetic derivatives have been examined for their inhibitory activity against HIV-1 integrase, and two pharmacophores associated with inhibition of this enzyme have been identified. A search of the NCI 3D database of approximately 200,000 structures yielded some 800 compounds which contain one or the other pharmacophore. Forty-two of these compounds were assayed for HIV-1 integrase inhibition, and of these, 27 had inhibitory IC50 values of less than 100 microM; 15 were below 50 microM. Several of these compounds were also examined for their activity against HIV-2 integrase and mammalian topoisomerase I.

In vitro activity of tylosin and its derivatives against Ureaplasma urealyticum.

Antimicrobial activity of tylosin (CAS 1401-69-0) and five other 16-membered macrolides biosynthesized by Streptomyces fradiae (lactenocin, desmycosin, macrosin (CAS 11049-15-3), relomycin (CAS 1404-48-4) and 5-O-mycaminosyl tylonolide) against Ureaplasma urealyticum was studied. The lowest minimum inhibitory concentrations (MIC) showed 5-O-mycaminosyl tylonolide, tylosin and descomysin. Absence of the aldehyde group in the structure of relomycin resulted in loss of the antimicrobial activity. Tylosin, desmycosin and macrocin proved better antimicrobial effect in the alkaline medium than in the acidic one.

Role of aliphatic acids in the biosynthesis of vermiculin in penicillium vermiculatum.

The diolode macrolide vermiculin (1) together with the three unsaturated aliphatic ketoacids vermiculinic (2), vermiculic (3) and 4-deoxovermiculic acid (4) were isolated from the cultivation broth of Penicillium vermiculatum. Biotransformation of 2 and 3 with growing and resting cells of P. vermiculatum was studied. We suppose, that 2 which is formed from 3, is the ultimate progenitor of 1.

Biotransformation of benzyl thiocyanate by Streptomyces aureofaciens.

Benzyl thiocyanate, a specific stimulator of chlortetracycline biosynthesis, was transformed into dibenzyl disulphide by Streptomyces aureofaciens. The disulphide stimulated chlortetracycline production to a lesser extent than did benzyl thiocyanate.

Metabolites of Pseudevernia furfuracea (L.) Zopf. and their inhibition potential of proteolytic enzymes.

Atranorin (1), physodic acid (2), oxyphysodic acid (3) and virensic (4) acid were identified in P. furfuracea, a lichen species collected in West Tatra. According to HPLC analysis contents of these metabolites in dried material was 0.11-0.19% (1), 1.46-3.78% (2), 1.69 to 3.44% (3), 1.14-1.46% (4). Atranorin was the strongest inhibitor of trypsin as well as of the porcine pancreatic elastase.

Vermiculin derivatives. Part 2: Cytotoxic and mutagenic activities of vermiculin derivatives.

The induction of mutations at the HPRT locus and cytotoxicities of 4 vermiculin derivatives 2-4 and 6 were examined in V79 Chinese hamster cells and compared with those of the parent compound vermiculin (1). Derivatives prepared by hydrogenation were less toxic and mutagenic or non toxic and non mutagenic. The substitution at position 13 affected the evaluated biological effects. The results suggest that in vitro metabolism of vermiculin resulted in decreased cytotoxicity and mutagenicity.

Vermiculin derivatives. Part 1: Synthesis of vermiculin derivatives.

Hydrogenation of the macrodiolide antibiotic vermiculin (1) over Adams catalyst afforded [8S, 16S]-8,16-bis(2'-oxopropyl)-1,9- dioxyacyclohexadeca-2,5,10,13-tetrone (2), [8S, 16S]-8,16-bis(2'-oxopropyl)-13-hydroxy-1,9-dioxacyclohexadeca- 2,5,10-trione (3), [8S,16S]-8,16-bis(2' oxopropyl)-1,9- dioxacyclohexadeca-2,5,10-trione (4) together with [7S]-4,9-dioxo-7-(4',9'-dioxodecanoyloxy)decanoic acid (5). Hydrogenation of diolide 1 over Pd/C gave tetrahydrovermiculin (2) only. The prepared compounds showed lower antibacterial and cytotoxic activities than vermiculin (1).

Aliphatic 1,2-alkanolamines--inhibitors of beta-glucanase from Candida utilis.

Aliphatic 1,2-alkanolamines inhibited beta-glucanase from Candida utilis. The highest inhibitory effect was observed with 1-dodecylamino-3-chloro-2-propanol (Ki = 1.0 mumol/L) and it was much higher than that of D-glucono-delta-lactone. Simple 1,2-alkanolamines, like 2-aminoethanol or 2-methylaminoethanol, did not exhibit any significant inhibitory effect.

Oxidation of brefeldin A.

Oxidation of the macrolide antibiotic brefeldin A with pyridinium chlorochromate adsorbed on alumina afforded [6S, 10E, 11aS, 14E]-6-methyl-2,3,6,7,8,9,11a,12-octahydro-4 H-cyclopent[f]oxacyclotridecin-1,4,13-trione together with 13-oxobrefeldin. These compounds showed higher cytotoxic activity on P388 leukemia cells than brefeldin A, brefeldin A-1,13-diacetate, brefeldin A-13-acetate, tetrahydrobrefeldin or tetrahydrobrefeldin-1,13-dione. 13-Oxobrefeldin exceeded brefeldin A in antifungal activity on Candida albicans.