In vitro activity of trimethoprim in association with sulfimidazole against aerobic gram-negative and gram-positive microorganisms and Clostridia.

The in vitro activity of a chemotherapeutic agent, sulfimidazole (SIZ), obtained by combining two molecules belonging to groups of extremely different antibacterial drugs, p-aminobenzene sulfonamide and a derivative with a 5-nitroimidazole ring, was studied. In association with trimethoprim, SIZ induces an intense synergistic antibacterial effect on gram-negative and gram-positive aerobic microorganisms and Clostridia. The results show that, in SIZ, the activity of each starting molecule remains unchanged providing that its structure-action relationship is kept intact.

IgG antibodies to papillomavirus genus-antigens in adult men with cancer of the urinary bladder.

Forty-five sera from men with bladder cancer were examined in a micro solid-phase enzyme-linked immunosorbent assay (ELISA) and in a Western-blotting (WB) assay for the presence of IgG antibodies to papillomavirus (PV) genus-antigens of bovine origin. The ELISA detected PV antibodies in 75.6% of cancer patients. This antibody frequency was significantly higher than that found in both healthy males (22.7%) and patients with urological disorders (24%). A similar correlation among the PV antibody frequencies of the three groups was found with WB assay: 60% of the neoplastic group showed PV antibodies versus 17.3% in healthy males and 32.6% in non-neoplastic patients. Within the same group, 78% to 87% sera showed the same reactivity to both assays. Of these concordant sera, PV positive sera were 55.6% in cancer patients, 13.3% in healthy adults and 19.6% in patients with urological disorders. ELISA PV antibody level in the cancer group was higher than in each of the two control groups. The meaning of the humoral response to PV genus-antigens in men with bladder cancer is discussed.

Synthesis and biological activity of new heterocyclic structures: [1,3]thiazino[2,3-i]purine, thiazolo[3,2-c] [1,2,3]triazolo[4,5-e]pyrimidine and [1,2,3]triazolo [4', 5': 4,5] pyrimido[6,1-b][1,3]thiazine.

Some derivatives of thiazolo[3,2-c]pyrimidine, pyrimido[6,1-b][1,3]thiazine, thiazolo[2,3-i]purine, [1,3]thiazino[2,3-i]purine, thiazolo[3,2-c][1,2,3]triazolo[4,5-e]pyrimidine and [1,2,3]triazolo[4',5':4,5]pyrimido[6,1-b][1,3]thiazine were prepared. The compounds were tested for antimicrobial and antimycotic activity on a number of strains, namely, Escherichia coli, Proteus vulgaris, P. mirabilis, Pseudomonas aeruginosa, Salmonella sp., Staphylococcus aureus, Streptococcus faecalis, Bacillus subtilis, Sarcina lutea, Candida albicans, Aspergillus sp., and for antiviral activity on Herpes simplex virus, Type 1 (HSV-1), Vesicular stomatitis virus (VSV) and Coxsackievirus B5 (CoxB5). The compounds proved to be devoid of activity against viruses, mycetes and gram-negative bacteria, while some of them exhibited a modest activity against gram-positive bacterial strains.

In vitro activity of sulphimidazole alone and in association with trimethoprim against enteric pathogens.

Sulphimidazole is a new sulphonamide belonging to the class of intestinal sulphonamides and characterized by the fact that it is active even in vitro. It has the heterocyclic ring of 5-nitroimidazoles on amidic nitrogen. Its antibacterial activity is similar to that of the classical sulphonamides but differs in that it also combats certain anaerobic bacteria such as Clostridium botulinum. This effect is completely absent in the case of sulphadiazine and sulphamethoxazole. Also, since p-amino-benzene-sulphonamide is present in the molecule, the drug acts in synergism with trimethoprim against certain aerobic or facultative strains of enteric pathogens.

Synthesis and biological activity of pyrimido[2,1-b][1,3]thiazine, [1,3]thiazino[3,2-a]purine and [1,2,3]triazolo[4,5-d][1,3]thiazino[3,2-a]pyrimidine derivatives and thiazole analogues.

Some series of thiazolo[3,2-a]pyrimidine, pyrimido[2,1-b] [1,3]thiazine, thiazolo[3,2-a]purine, [1,3]thiazino[3,2-a]purine, thiazolo[3,2-a][1,2,3]triazolo[4,5-d]pyrimidine and [1,2,3]triazolo[4,5-d][1,3]thiazino[3,2-a]pyrimidine derivatives, variously functionalized, were prepared. The compounds were tested for antimicrobial and antimycotic activity on a number of strains, namely: E. coli, Proteus vulgaris, P. mirabilis, Pseudomonas aeruginosa, Salmonella sp., Staphylococcus aureus, S. faecalis, Bacillus subtilis, Sarcina lutea, Candida albicans, C. tropicalis, Aspergillus sp., and for antiviral activity on Herpes simplex virus Type 1, Vesicular stomatitis virus and Coxsackievirus B5. The compounds proved to be devoid of activity against viruses and gram-negative bacteria, while some of them exhibited modest activity against gram-positive bacterial strains.

Antimycotic action of methyl substituted N-(5-pyrimidinyl)benzenesulfonamide derivatives.

Some series of N-(5-pyrimidinyl)benzenesulfonamide variously methylated at the ring and/or sulfonamidic nitrogens and substituted at the benzene with NO2 or NH2 were synthesized and studied spectrometrically (N.M.R). When tested on several strains of Candida albicans and Candida tropicalis, some of the compounds exhibited very slight antimycotic activity.

Antimycotic action of alkyl derivatives of 5-(benzenesulfonamide)-1,2,3,4-tetrahydro-2-thioxo-4-pyrimidinon e.

Several series of mono-, di- and trimethyl derivatives of N-(6-amino-1,2,3,4-tetrahydro-4-oxo-2-thioxo-5-pyrimidinyl)benzene sulfonamide substituted at the benzene ring (Z), were synthesized and studied spectrophotometrically. The spectral and physical data enabled the structures of the methyl derivatives obtained by methylating (Z) to be identified. When assayed biologically as antimycotics, a small percentage of the substances exhibited mild fungicide activity.

Antimycotic action of some amino-N-(5-pyrimidinyl)benzenesulfonamides.

2-, 3- and 4-amino-N-(6-amino-1,4-dihydro-4-oxo-2-mercapto (or alkylthio)-5-pyrimidinyl)benzenesulfonamides were synthesized and biologically tested on different strains of Candida albicans and Candida tropicalis. Some of the 4-aminoderivatives were also tested for antibacterial properties on numerous bacterial strains. Antimycotic activity of 4-amino compounds, expressed as MIC, is around 50 micrograms/ml and higher than that of both 2-amino- and 3-aminoderivatives. In all these compounds alkyl chain length does not seem to have any notable effects on biological activity, an exception being made for some aralkyl compounds. Antibacterial activity of 4-aminoderivatives is very low for all strains tested.

[Molecular structure with potential inhibitory action on the biosynthesis of FAH4]. / Strutture molecolari a potenziale azione inibitrice della biosintesi del FAH4.

Molecules formed by two pharmacophoric synthons--4-H2N--C6H4--SO2NH--and 2,4-diaminopyrimidine--were prepared. These structural units, with sulphamidic and antifolic action respectively, are bound without mutual electronic interaction, as demonstrated by their experimental electronic indices. The compounds were tested for activity on several bacterial strains and their biological activity was compared with that of molecular combinations formed by 4-aminobenzensulphonamide and substituted 2,4-diaminopyrimidines, to discover whether these two pharmacophoric synthons, so bound, are synergic.