Biomedical subjects
Publications and source records attributed to N Simonetti.
The amount of glycogen in vaginal liquids decreases with Trichomonas vaginalis and this is connected with T. vaginalis activity in specimens. A glycogen-hydrolysed casein medium ("glycogen medium") added to vaginal liquid is a valid maintenance medium for T. vaginalis and therefore enables a direct test for antitrichomonas drugs to be performed.
We have investigated the possibility of vaginal liquids affecting the transition from a yeast form (Y) to a mycelial one (M) in C. albicans and the possible relation to microbial flora, pH and glycogen. The C. albicans Y----M conversion, "mycelial vaginal test", in 250 specimens of vaginal liquid shows a 70% positivity rate against a test Candida strain. Results of the vaginal test are not related to bacteria, flora and pH, but to Candida infection and to glycogen concentration. Using a Y----M good-responder Candida strain in the vaginal test it is possible to have a global index of the factors affecting the Candida filamentation in the host. It can be advisable to utilize the vaginal test as a virulence test for Candida strains and as an indicative test of phenotypic drug resistance.
The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported. Antimicrobial data in comparison with pyrrolnitrin show that N-methylpiperazinylamides exhibit very poor activity against Candida albicans and Candida sp. while acid and ester derivatives are inactive. Vice-versa many acid or amide derivatives show interesting antibacterial activity. The results obtained are discussed on the basis of structure-activity relationships.
Chlorhexidine increases the activity of itraconazole against Candida isolates; itraconazole-chlorhexidine combinations show synergistic activity in culture media. The activity of itraconazole is discussed.
Itraconazole was found to be superior to ketoconazole in its antifungal activity in vitro against Hyphomycetes and Candida. In particular, complete inhibition of germination of Candida albicans and Aspergillus spp. by a lower dose of itraconazole can explain the better activity in vivo of this drug.
The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported. Antimicrobial data in comparison with pyrrolnitrin show that only carboxamide derivatives exhibit satisfactory antifungal activity. By contrast all tested compounds show very poor antibacterial activity. The displacement of NO2 group from para to meta or ortho position of the aryl at C5 of the pyrrole ring affects the antimicrobial activity.
The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported. The N-methylpiperazinyl substituent must be regarded as fundamental to activity. Furthermore the presence of substituents on the para position of the two phenyl rings and the presence of halogen atoms can be considered strengthening factors to microbiological activity. The results obtained are discussed on the basis of structure-activity relationship.
The synthesis and antifungal activities of pyrrole analogues of bifonazole are reported. Reduction of 4-nitrobenzophenone to the corresponding alcohol, reaction with phosphorus tribromide of the latter compound and condensation of the bromonitroderivative with imidazole led to 1-[alpha-(4-nitrophenyl)-4'-benzyl]-1H-imidazole. Hydrogenation of the nitro group to amino and reaction with 2,5-dimethoxytetrahydrofuran according to the Clauson-Kaas procedure afforded the pyrrole analogue of bifonazole. This compound and the related chloroderivative were also prepared by a similar pathway starting from 4-(1H-pyrrol-1-yl)benzophenone and its 4'-chloroderivative. Microbiological screening against Candida albicans and Candida spp showed 1-(alpha-[4-(1H-pyrrol-1-yl)phenyl]benzyl)-1H-imidazole to be the most active compound among the tested derivatives.
LY121019 is a cyclic peptide antibiotic of the echinocandin group, which is characterized by strong anti-Candida activity (in particular against Candida albicans) as well as by low experimental toxicity. Its anti-Candida activity is thought to be due to an inhibition of the synthesis of beta-glucan, an essential cell wall polysaccharide. The different composition of culture media or the presence of animal serum did not show adverse effects on LY121019's anti-Candida activity and the addition of reducing compounds such as cysteine and hydroquinone did not manifest a negative influence. Analogously the anti-Candida activity was not influenced when C. albicans was grown under aeration. The activity of LY121019 was very high against the mycelial form of C. albicans even when this form was developed in the presence of animal serum.
Some (1-pyrryl)methyl derivatives of 1-ethyl-1,4-dihydro-4-oxoquinoline-3-carboxylic acid were synthetized by the standard procedure involving Gould-Jacobs and Lappin reactions. The above derivatives were tested microbiologically as nalidixic acid analogs and compared with some clinically useful 4-oxopyridine-3-carboxylic acids (nalidixic acid, pipemidic acid, norfloxacin, enoxacin and ciprofloxacin). Their antibacterial activities were very weak.
Some p-methylbenzolpyrrole acrylic acids and related compounds were synthesized. The new pyrrole derivatives have structural features in common with trichostatin A, an antifungal antibiotic. The above acids and derivatives were tested against Candida albicans and Candida sp in comparison with miconazole, pyrrolnitrin and amphotericin B and showed very weak antifungal activities. Occasionally some activity was found against a few strains of Candida albicans and against Candida pseudotropicalis.
A new route to pirfloxacin, a fluorinated pyrrylquinolone with high broad-spectrum antibacterial activities, is described starting from 7-amino-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 2,5-dimethoxytetrahydrofuran. When the reaction with the latter compound was carried out using the ethyl ester of the above acid the related pyrryl ester formed, which on alkaline hydrolysis gave pirfloxacin. The synthesis and antibacterial activities of the 1-allyl analogue of pirfloxacin and of 7-[2-(1-pyrrolidinomethyl)-1-pyrryl]-1-ethyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid and its 6-fluoroderivative are also reported.
The analysis of the results obtained in our trials, which took into account different experimental conditions, suggests that ketoconazole is a very effective anti-Candida drug. In particular, ketoconazole inhibits the development of the hyphal form of C. albicans which is highly invasive. In our trials, we were also able to demonstrate that it is possible to extend ketoconazole's range of action to gram-negative bacteria, if the drug is used in appropriate pharmaceutical forms. Moreover, its in vivo efficacy against dermatophytes and ifomycetes can also be explained by its ability to concentrate in keratinized tissues. From the investigations carried out on leukocyte populations, it has also been demonstrated that ketoconazole does not negatively interfere with the cell defense mechanisms of the host. In fact, the opsonic index and intraphagocytic killing do not significantly change in the presence of ketoconazole in therapeutic doses.
The synthesis and antifungal activities of many derivatives of 1-(2-imidazolylmethyl)aniline and of 1-(4-imidazolylmethyl)aniline are reported. Antimicrobial data in comparison with miconazole show that many compounds containing chlorine atoms and nitro group exhibit an interesting antimycotic activity. The results obtained are discussed on the basis of structure-activity relationships.
The synthesis and antifungal activities of 1-aryl-4-p-nitrophenylimidazoles and their 2-mercaptoderivatives is reported. Antimicrobial data in comparison with antifungal antibiotic pyrrolnitrin attributed the best activity to 1-p-methoxyphenyl-4-p-nitrophenylimidazole. The tested compounds were prepared by reacting p-nitrophenacylanilines with potassium thiocyanate in acidic medium to afford 1-aryl-2-mercapto-4-p-nitrophenylimidazoles, which were then transformed into the title compound by treatment with nitric acid.
Fructose-1,6-diphosphate (FDP) exerts a marked activity on reticuloendothelial system (RES) functions, increasing in mice the clearance of colloidal carbon. ATP depletion occurring during phagocytic activity is concentrated by FDP.
The synthesis of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1H-pyrrol-1-yl)quinoline-3-carboxy lic acid, a new fluorinated high broad-spectrum antibacterial agent related to nalidixic acid is described. The title compound has been prepared by the reaction of 4-fluoro-3-(1H-pyrrol-1-yl)aniline with diethyl ethoxymethylenemalonate, cyclization of the malonate obtained to the quinolinecarboxylate ester, ethylation of the ester, followed by hydrolysis with aqueous sodium hydroxide. The new derivative proved very active against both gram-positive and gram-negative bacteria. Its activities in comparison with those of nalidixic acid, pipemidic acid, piromidic acid and enoxacin were found to be greatly superior with regard to the unfluorinated compounds and somewhat superior also to enoxacin. The known 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(pyrrolidin-1-yl)quinoline-3- carboxylic acid, here prepared by catalytic hydrogenation of the pyrrole moiety of the title compound, has been found to be less active as an antibacterial agent.
The synthesis of analogues of antifungal econazole with a pyrrole moiety starting from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanone and from 1-(4-chlorophenyl)-2-(1H-pyrrol-1-yl)ethanol is described. Results of antimicrobial screening of the new derivatives in comparison with econazole are also reported.