Antimicrobial agents

In a study of the effect of progesterone, its hydroxy derivatives and various sterols on the growth of dermatophytes, it was demonstrated that all the steroid compounds employed inhibited growth of the 51 strains of dermatophytes tested. No significant differences were found in sensitivity to the given steroids, either in dermatophyte strains of the same species, but of different origin, ior in different species of the four genera used (Trichophyton, Microsporum, Epidermophyton andKeratinomyces). Hydroxylation of the progesterone molecule in any except the C-21 position lowered the inhibitory effect. The course of the transformation reaction on the progesterone or cholesterol molecule was likewise of a uniform character from the aspect of species specificity. Progesterone was simultaneously hydroxylated in positions 15α and 15β by all the strains, giving rise to monohydroxy-derivatives as the main metabolites, and cholesterol was oxidized to cholestenone.     

Antimicrobial agents

The development of acquired, temporary resistance induced by an adaptation mechanism as a result of direct contact of the cell with an antimycotic, was demonstrated in pathogenic species of the genusCandida. Acquired resistance induced by one substance was manifested in multiresistance to other, structurally quite different, antimycotics. Cultivation of the strain on antimycotic-free medium led to relatively rapid deadaptation and the strain regained its initial sensitivity. The sensitivity of adapted and deadapted strains was studied by the dilution method (determining MIC values) and by the “direct” Warburg method (evaluating metabolic quotients).     

Antimicrobial agents

The antimicrobial effectivity of 32 derivatives and analogues of 10-(4-methylpiperazino)-10,11-dihydrodibenzo(b,f)thiepine was investigated and it was found that substituents in rings A and C and in the piperazine residue affect the antimicrobial potency of the compound. The derivative with the chlorine atom in position 3 was found to be most active in suppressing microbial growth. Substitution with chlorine of the ring C in positions 6, 7 and 8 produced derivatives with highest tuberculostatic activity. The growth of Gram-negative microorganisms (with the exception ofKlebsiella pneumoniae), as well as of fungiTrichophyton mentagrophytes, Candida albicans andAspergillus niger, was not suppressed by any of the derivatives. The antimicrobial effect of the active derivatives was demonstrated on strains ofStreptococcus haemolyticus, Staphylococcus pyogenes aureus, Mycobacterium tuberculosis, Klebsiella pneumoniae andSaccharomyces pastorianus.     

Antimicrobial agents

The effect of 2-aminotridecane and its addition salts with different substituted phenols on growth ofCandida albicans was studied and the fungistatic and fungicidal activity of these substances was compared. The addition 2-aminotridecane salts with 2,4,5-trichlorophenol and with 2-chloro-4-introphenol were found to be the most active in all three tests. The activity of the other addition salts tested differed little from that of actual 2-aminotridecane.     

Antimicrobial agents

The adaptation of dermatophytes to antimycotics leads to the development of two independent processes—the induction of degrading enzyme systems detoxicating the antimycotic to less active or completely inactive derivatives, and temporary resistance, accompanied by increasing loss of sensitivity of the dermatophytes to the given antimycotics. These processes can both be regarded as part of the defences of the microbial cell.     

Antimicrobial agents

In the microbial transformation of 2-chloro-4-nitrophenol and its 2-aminotridecane compound salt, 2-chloro-4-nitrophenol was found to be degraded to four metabolites only on using strains resistant to 2-chloro-4-nitrophenol. Sensitive strains lacked this property. In the case of the 2-amino-tridecane compound salt, the first reaction produced by strains resistant to 2-chloro-4-nitrophenol was dissociation of the compound salt into the two initial components, followed by degradation of 2-chloro-4-nitrophenol. Microbial degradation resulted in diminished antifungal activity. The other antimicrobi-ally active component of the compound salt, i.e. 2-aminotridecane, was not affected by biotransformation and kept its original activity.     

Antimicrobial agents

In the microbial degradation of Fungicidin by lower pathogenic fungi, no significant differences were found in the rate of its degradation by the various species of dermatophytes employed (Trichophyton mentagrophytes, Trichophyton rubrum andMicrosporum gypseum), but there was a marked difference in the rate of enzymatic degradation by microorganisms adapted and not adapted to Fungicidin or Amphotericin B. After four hours' degradation of Fungicidin by non-adapted strains, about 70% of the Fungicidin in the medium was still intact, whereas it was completely degraded by adapted strains during the same interval. The addition of protein biosynthesis inhibitors (chloramphenicol and tetracycline) and of the antifungally active substance 2-aminotridecane did not influence the microbial degradation of Fungicidin by dermatophytes.