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The results of the study on the inhibitory effect of a number of rifamycin derivatives, such as rifamycin B, rifamycin O, rifamycin, rifamycin A, 25-desacetylrifampicin and rifampicin are presented. It was shown that rifampicin had the highest inhibitory effect on the synthesis of RNA in the cells of E. coli and Staph. aureus. It inhibited the above process by 93.0 and 98.8 per cent respectively. The data on the cells of Staph. aureus, as well as the data on comparison of the inhibitory effect of rifampicin derivatives with respect to the RNA-polymerase reaction in acellular systems are presented.

Competing interaction of two novel N-acyl derivatives of ampicillin i.e. N'-benzylchlorbenzimidazole (No. 48) and N-pyrazolytiazole (No. 72) derivatives and 14C-benzylpenicillin with penicillin-binding proteins (PBP) of E. coli was studied. It was shown that ampicillin and its derivative No. 48 markedly differed in their affinity to various PBPs. Derivative No. 72 did not prevent binding of the labeled benzylpenicillin to any PBP which corresponded to its low antimicrobial activity. Analogous experiments with new cephalosporin structures i.e. active and inactive N-acyl derivatives of cephalosporin showed that the active derivative No. 94 i.e. N-methyltiobenzimidazole derivative had the highest affinity to PBP-2 and PBP-5. The inactive derivative No. 68 i.e. N-chlorbenzimidazole derivative also had high affinity to PBP-1b, PBP-2 and PBP-3 essential for the cell. No activity of the latter compound against intact cells of E. coli was probably due to its low penetration through the outer membrane of the bacterial cell. Estimation of affinity of the beta-lactam structures to various PBPs not only provided data on the mechanism of their action but also made it possible to explain in some cases the peculiarities of their antimicrobial spectrum.

It was shown that preincubation of E. coli intact cells with gentamicin and streptomycin induced a marked increase in binding of 14C-benzylpenicillin to its final targets in the membrane i.e. penicillin-binding proteins (PBP). The stimulating effect of the aminoglycosides was also confirmed in experiments with a membrane fraction isolated from the cells preincubated with the aminoglycosides. The PBPs of the cells preincubated with the aminoglycosides were studied with SDS-PAAG electrophoresis. It was revealed that under the action of the aminoglycosides the quantity of the labeled substance (intensity of the bands on the fluorograms) fixed by the low molecular PBPs i.e. D-alanine carboxypeptidases increased. Moreover, the composition of the high molecular less mobile PBPs (transpeptidases) changed. The data are discussed in regard to the peculiarities of the effect of the aminoglycosides on the cells (bactericidal action, membrane tropism). The effect of the aminoglycosides can influence (along with the others) the results of their combined use with beta-lactams.