Association of anthracycline derivatives with DNA: a fluorescence study.

The DNA affinity for 26 anthracycline derivatives was studied by the quenching fluorescence technique. The stereochemical requirements for DNA intercalation are discussed. The relationship between the DNA affinity and bioactivity is also pointed out.

Radioisotopic and synthetic studies related to caroxazone metabolism in man.

Labelled 2-oxo-2H-1,3-benzoxazine-3(4H)-acetamide (caroxazone), has been synthesized by condensing N-(2-hydroxylbenzyl/glycinamide with 14C phosgene. Metabolic studies were performed administering the labelled drug to man and recovering metabolites from the urines. Beside the unchanged drug, five metabolites were identified and confirmed by synthesis, namely (3,4-dihydro-3-carboxamidomethyl-2-oxo-2H-1,3-benzoxazin-4-yl)urea (IX), N-carboxamidomethyl o-hydroxymethylphenyl carbamate (V), 4-methoxy-2-oxo-2H-1,3-benzoxazine-3(4H)acetamide (VIIIa), 2-oxo-2H-1,3-benzoxazine-3(4H)acetic acid (III) and 4-hydroxy-2-oxo-2H-1,3-benzoxazine-3(4H)acetamide (IV).

On the mechanism of inhibition of enzyme induction in Escherichia coli by distamycin A.

The mechanism of the interference of the antiviral antibiotic distamycin A with the bacterial cell has been investigated. Labelled distamycin A is firmly bound by E. coli cells and the binding process does not require metabolic energy as indicated by the use of inhibitors. The antibiotic does not induce gross alteration in the cell membrane but inhibits cyclic AMP accumulation in the cells exposed to a glucose-free medium. This inhibition is concomitant with that exerted on the synthesis of an inducible enzyme such as beta-galactosidase. By the method of pulse induction it appears that distamycin A exterts its inhibiting effect on inducible synthesis at the level of transcription. This effect is probably related to an interference with the positive control of enzyme synthesis performed via the system represented by cyclic AMP and the CRP protein.