Production of the antitumor drug epirubicin (4'-epidoxorubicin) and its precursor by a genetically engineered strain of Streptomyces peucetius.

A fermentation method that bypasses the low-yielding semisynthesis of epirubicin (4'-epidoxorubicin) and 4'-epidaunorubicin, important cancer chemotherapy drugs, has been developed for Streptomyces peucetius. This bacterium normally produces the anthracycline antibiotics, doxorubicin and daunorubicin; the 4'-epimeric anthracyclines are formed by introducing the heterologous Streptomyces avermitilis avrE or Saccharopolyspora eryBIV genes into an S. peucetius dnmV mutant blocked in the biosynthesis of daunosamine, the deoxysugar component of these antibiotics. Product yields were enhanced considerably by replacing the chromosomal copy of dnmV with avrE and by introducing further mutations that can increase daunorubicin and doxorubicin yields in the wild-type strain. This method demonstrates that valuable hybrid antibiotics can be made by combinatorial biosynthesis with bacterial deoxysugar biosynthesis genes.

Concentrations of flurithromycin in serum and tonsils.

The concentrations of flurithromycin in serum and palatine tonsils of eleven adult male patients undergoing tonsillectomy were determined. Each patient received 500 mg t.i.d., in all ten doses, before tonsillectomy. Flurithromycin concentrations were measured by a microbiological method. Mean serum levels (+/- SE) were 0.72 microgram/ml (+/- 0.19) after 8 h from the 9th dose and 0.67 microgram/ml (+/- 0.13) after 4 h from the 10th dose. Average concentrations (+/- SE) in tonsils were: 1.43 +/- 0.20 microgram/g (right) and 1.32 +/- 0.21 (left) 4 h after the last administration. Therefore, the mean tissue/serum ratio was about 2:1. These results indicate a good diffusion of flurithromycin from serum to tonsillar tissue.

Synthesis of some derivatives of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)-3-quino linecarbo xylic acid (norfloxacin) as potential antibacterial agents.

Twelve new fluoroquinolones, structurally related to norfloxacin, have been synthesized in order to investigate the effect of substituents at the secondary nitrogen of the piperazine ring on antimicrobial activity. The new substances (carbamates, isoureas, guanidines, ureas and cyanamides) tested on a variety of gram-positive and gram-negative organisms showed lower activity than the model compound.

New fluorinated erythromycins obtained by mutasynthesis.

Following the previously described semisynthetic preparation of new aglycones (8S)-8-fluoroerythronolide A (I), (8S)-8-fluoroerythronolide B (II) and the monoglycoside 3-O-mycarosyl-(8S)-8-fluoroerythronolide B (III), their conversion into new fluoroerythromycins was attempted by mutational biosynthesis. The strain Streptomyces erythraeus ATCC 31772, a mutant blocked in the biosynthesis of erythromycin, was employed in the present investigation. Four new antibiotics, (8S)-8-fluoroerythromycin A (IV), (8S)-8-fluoroerythromycin B (V), (8S)-8-fluoroerythromycin C (VI) and (8S)-8-fluoroerythromycin D (VII) were successfully derived by such an approach. The result is also discussed in terms of the substrate specificity of the enzymes involved in the biosynthesis of erythromycins. The new antibiotics exhibited promising biological properties.

New cephalosporins and 7 alpha-methoxy cephalosporins. Chemistry and biological activities.

The synthesis and the in vitro activity of a number of cephalosporins and 7 alpha-methoxy cephalosporins having 7-acyl substituents derived from 1-methyl-4 (or 5)-nitro-1H-imidazolyl-thioacetic acids are described. The microbiological profile is influenced by the position of both the nitro group and the side-chain sulfur atom on the 1-methyl imidazole, and by the nature of the 3-substituent.

[Anti-mycoplasmatic activity of 2 antracyclinic antibiotics]. / Attivita' antimicoplasmatica di due antibiotici antraciclinici

The antimycoplasma activity (bacteriostatic and bactericidal) of daunomycin and adriamycin has been tested on 14 strains in liquid and solid medium. The minimal inhibitory concentration (MIC) values of daunomycin and tetracycline have resulted of the same greatness, while those regarding adriamycin are lightly greater.

[Comparison of the antibacterial activity in vitro of a combination of penicillin and other antibiotics on 127 strains isolated in an Oncological Institute]. / Confronto di attivitá antibatterica "in vitro" tra una associazione di penicilline ed altri antibiotici su 127 ceppi isolati in un Istituto Oncologico

127 pathogenic, opportunist and saprophytic strains isolated from patients and material in a Milanese oncological department were tested. An association of Ampicillin and Dicloxacillin ana (Diamplicil) proved effective against all strains, particularly Gram-negative bacteria notoriously responsible for hospital infections. A statistically inferior performance was observed for Rifampicin and Cephaloridine.