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A Malabarba

Publications and source records attributed to A Malabarba.

34 records · Page 2Linked to original sources
PubMed1989

Synthesis and biological evaluation of de(acetylglucosaminyl)didehydrodeoxy derivatives of teicoplanin antibodies.

A series of 34-de(acetylglucosaminyl)-34-deoxy derivatives of 34,35- and 35,52-didehydro teicoplanin antibiotics have been synthesized from teicoplanin and its N-acetylglucosamine containing pseudoaglycons under basic conditions. The structures of these compounds have been determined by 1H NMR, UV, and FAB-MS. 35,52-Unsaturated derivatives maintained in vitro and in vivo antimicrobial activity to a different extent as well as the ability for binding to Ac2-L-Lys-D-Ala-D-Ala, a bacterial cell-wall model for the site of action of glycopeptide antibiotics. In contrast, 34,35-unsaturated compounds were markedly less active and possessed a negligible affinity for the synthetic tripeptide.

Acetylglucosamine↗
PubMed1989

Synthesis and biological properties of N63-carboxamides of teicoplanin antibiotics. Structure-activity relationships.

The condensation of the carboxyl function of teicoplanin A2 (CTA) and its acidic hydrolysis pseudoaglycons (TB, TC) and aglycon (TD) with amines carrying various functional groups and chains produced amide derivatives with different isoelectric points and lipophilicities. Amide formation did not affect the ability of these compounds to bind to Ac2-L-Lys-D-Ala-D-Ala, a model for the natural peptide binding site in bacterial cell walls. The antimicrobial activities of teicoplanin amides were found to depend mostly on their ionic and lipophilic character and on the type and number of sugars present. Positively charged amides were generally more in vitro active than the respective unmodified antibiotics against Gram-positive organisms. In particular, most basic amides of CTA were markedly more active than teicoplanin against coagulase-negative staphylococci. A few amides of TC and most of those of TD also showed a certain activity against Gram-negative bacteria. In experimental Streptococcus pyogenes septicemia in the mouse, some basic amides were more active than the parent teicoplanins when administered subcutaneously. Some of those of CTA were also slightly more effective than teicoplanin by oral route.

Amides↗
PubMed1989

Dechloro teicoplanin antibiotics.

Mono- and didechlorinated derivatives of the antibiotic teicoplanin, its pseudoaglycones and aglycone, and of one amide and ester of deglucoteicoplanin were prepared under selective reductive conditions. The selectivity and rate of dehalogenation were studied and compared to those of vancomycin and deglucovancomycin. The influence of the chlorine substituents on the mechanism of action and antibacterial activity of teicoplanin antibiotics was also investigated.

Animals↗
PubMed1989

Synthesis and biological activity of N63-carboxypeptides of teicoplanin and teicoplanin aglycone.

A series of peptide derivatives of teicoplanin A2 (CTA) and deglucoteicoplanin (TD) was prepared by condensation of the 63-carboxyl function with the alpha-amino group of selected amino acids and their derivatives. The modification of the ionic character of CTA and TD influenced their in vitro and in vivo antimicrobial properties to a different extent, depending on the structure of the amino acidic moiety at C-63. A certain effect on binding strength to Ac2-L-Lys-D-Ala-D-Ala, a synthetic model of the antibiotic's target peptide, was also observed.

Animals↗
PubMed1987

Synthesis and biological activity of some esters of the N-acetylglucosaminyl aglycone and of the aglycone of teicoplanin.

A series of ester derivatives of teicoplanin-N-acetylglucosaminyl aglycone (T-A3-2) and deglucoteicoplanin was prepared starting from teicoplanin and from the corresponding deglycosylation compounds. The modification of the ionic and lipophilic character of the parent antibiotic strongly influences the spectrum of antibacterial activity in vitro.

Anti-Bacterial Agents↗
PubMed1987

Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VIII. Opening of the polypeptide chain of teicoplanin aglycone under hydrolytic conditions.

Hydrolysis of teicoplanin (a complex of five closely related factors plus one, more polar component) under selected conditions (acids in a biphasic hydroalcoholic medium) gives the single aglycone with good yields. When the reaction is carried out in homogeneous hydroalcoholic phase the removal of the sugars yields two new compounds. On the basis of fast atom bombardment mass spectra (FAB-MS), acid-base titration, IR, UV and 1H NMR analyses it has been demonstrated that these compounds are two diastereoisomers; they differ from the teicoplanin aglycone in having additional carboxyl and amino groups derived from the hydrolysis of an amide bond. Although the molecular shape of the new aglycones is greatly modified, they still maintain some antibacterial activity which might be correlated with residual binding ability towards the terminal D-alanyl-D-alanine residue of the cell-wall mucopeptides.

Actinomycetales↗
PubMed1986

Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VII. Preparation and NMR characteristics of the aglycone of teicoplanin.

Several hydrolytic reactions that transform teicoplanin or its pseudo-aglycones into the aglycone with good yields are described. The most interesting approach is hydrolytic removal of the sugars in benzyl alcohol with the formation of the aglycone benzyl ester which is then submitted to hydrogenolysis. A detailed description of the 1H and 13C NMR spectra of the teicoplanin aglycone hydrochloride is presented. All the signals were attributed to the hydrogen and carbon atoms using homo and heteronuclear COSY. The relevant interactions through space between the hydrogen atoms were obtained by NOE. The structural aspects are discussed in terms of the well-known mechanism of action of the glycopeptide antibiotics.

Anti-Bacterial Agents↗
PubMed1985

Physico-chemical and biological properties of actagardine and some acid hydrolysis products.

Actagardine (originally designated as metabolite B or gardimycin) is a polypeptide antibiotic produced by fermentation of Actinoplanes strains ATCC 31048 and 31049. During the course of repeated fermentations two new compounds, coded D and E, were isolated. Some physico-chemical and biological characteristics of actagardine and of both compounds are presented. Compound D is derived from chemical transformation of actagardine.

Animals↗
PubMed1984

Synthesis and in vitro biological evaluation of N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosamino)-L-alanine (L-alanosine AICO ribonucleoside).

L-Alanosine [3-(hydroxynitrosoamino)-L-alanine] is an antitumor antibiotic that at the present is undergoing phase II clinical trials. Its mode of action as well as its metabolism has been extensively studied, and the metabolite N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosoamino)-L-alanine ribonucleotide (L-alanosine AICOR) proved to be an extremely potent inhibitor of de novo purine biosynthesis and is thus primarily responsible for the antitumor activity of the drug. The synthesis of the corresponding ribonucleoside, i.e., N-[(5-amino-1-beta-D-ribofuranosyl-1H-imidazol-4-yl)carbonyl]-3- (hydroxynitrosamino)-L-alanine ribonucleoside (L-alanosine AICO ribonucleoside), was accomplished by condensation of a suitably protected derivative of L-alanosine with N-succinimidyl-5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-1H-im idazole-4-carboxylate followed by the removal of the protective groups. The biological activity of L-alanosine AICO ribonucleoside was tested in vitro on whole tumor cells and on the isolated enzyme adenylosuccinate synthetase and in vivo on murine experimental leukemia. The compound was found to be inactive in these tests.

Antibiotics, Antineoplastic↗
PubMed1984

Teicoplanin, antibiotics from Actinoplanes teichomyceticus nov. sp. VI. Chemical degradation: physico-chemical and biological properties of acid hydrolysis products.

Teicoplanin is an antibiotic complex consisting of five closely related factors, T-A2-1, 2, 3, 4 and 5 and a more polar factor, T-A3-1. By controlled acid hydrolysis the complex is transformed into pseudoaglycones and finally into a single aglycone with consecutive removal of three sugar units. Quantitative determination of sugars obtained by degradative reactions and NMR/LC-MS studies on suitable derivatives confirmed that all the components carry one N-acyl-D-glucosamine and that at least two of them are characterized by N-decanoyl and N-undecanoyl chains on the D-glucosamine unit. The hydrolysis products still possess in vitro and in vivo activity.

Animals↗
PubMed1984

7-(D,L-alpha-fluoro-2-thienylacetamido)cephalosporanic acid (L 14655), a new semisynthetic cephalosporin. Synthesis and preliminary biological evaluation.

We describe the synthesis and some preliminary antimicrobial and enzymatic properties of 7-(D,L-alpha-fluoro-2-thienylacetamido)cephalosporanic acid (L 14655), a fluorinated derivative of cephalothin. L 14655 had antimicrobial activity similar to that of cephalothin. Cell-free studies demonstrated that L 14655 was very stable to hydrolysis by type Ia beta-lactamase (325 times more than cephalothin) but not to TEM enzyme. In addition, L 14655 was 480 times more active than cephalothin in preventing the hydrolysis of nitrocephin by type Ia enzyme. Preliminary studies in intact beta-lactamase-producing cells did not however produce evidence of enhanced activity of L 14655 relative to cephalothin.

Anti-Bacterial Agents↗
PubMed1984

Inhibitory activity and resistance to hydrolysis by beta-lactamases of some (D,L)-7-(alpha-fluoroacylamino)cephalosporins.

The synthesis of a series of (D,L)-7-(alpha-fluoroacylamino)-cephalosporanic acids are described. In vitro antimicrobial activity was determined in comparison with the corresponding non-fluorinated compounds. None of them were found to be better than clinically used cephalosporins. Resistance to and inhibition of beta-lactamases from gram-negative organisms were also determined. All the fluorinated derivatives were found to be as resistant to hydrolysis by Escherichia coli R+TEM beta-lactamase as the corresponding non-fluorinated compounds, but resulted more resistant (from 2.3 to 61.2 times) to Enterobacter cloacae 214 beta-lactamase. Title compounds were also found to be better inhibitors of E. cloacae 53 and E. cloacae 214 beta-lactamases than the related non-fluorinated cephalosporins.

Bacteria↗
PubMed1979

[Synthesis and biological activity of 7-(2-nitroimidazoles and 7-(2-aminoimidazole) methyleneamino cephalosporin and their derivatives].

The synthesis of 7-[[(1-methyl-2-nitro-1H-imidazol-5-yl)methylene]amino] and 7-[[(2-amino-1-methyl-1H-imidazol-5-yl)methyle-ne]amino]cephalosporanic acids and of some derivatives is described. Their physico-chemical characteristics are reported. The compounds show no appreciable antibacterial activity in vitro. They show no synergy with cephaloridine against Enterobacter cloacae 214 (producer of class I beta-lactamase) and therefore have no anti-beta-lactamase activity.

Cephalosporins↗
PubMed1978

Synthesis and biological activities of some cephalosporin derivatives with carbonylamino or acetylamino [(nitro or amino) imidazole] substituents in position 7.

The synthesis and the physicochemical properties of some cephalosporin derivatives with a carbonylamino- or acetylaminoimidazole moiety in position 7 are described. The effects on biological activity of the presence of some groups (methyl or ethyl, 2-nitro or 5-nitro, 2-amino) on the imidazole nucleus are examined. Selected heterocyclicthiomethyl substituents were also introduced in the 3 position of the cephalosporin nucleus. The in vitro antimicrobial activities of the compounds and their effectiveness in protecting against bacterial (S. aureus) infections in mice were evaluated. Two of the compounds (V b) and (V d) are as active as cephalexin and more active than cephalothin when administered subcutaneously, while they appear to be less effective when administered orally.

Animals↗
PubMed1977

Synthesis and biological activities of some 7-(1,2,4-oxadiazolylacetylamino) cephalosporins.

The synthesis and the physico-chemical properties of cephalosporin derivatives carrying an (1,2,4-oxadiazol-3-yl)- or (1,2,4-oxadiazol-5-yl)acetylamino moiety in position 7 are described. The effects of the presence of an amino or hydroxyl group on the oxadiazole ring are examined. Selected heterocyclicthiomethyl substituents are also introduced in the 3 position of the cephalosporin nucleus. In vitro antimicrobial activity and effectiveness in protecting against bacterial infection in the mouse are evaluated. Only compound (V b) was found to have slight activity when compared with cephalosporins in clinical use.

Acylation↗