N. Simonetti

Antifungal agents. 1. Synthesis and antifungal activities of estrogen-like imidazole and triazole derivatives

Abstract The synthesis of some 2-aryl-1-(4-methoxyphenyl)-1-(1 H -imidazol-1-yl)ethane derivatives and related 1 H -1,2,4- and 1 H -1,3,4-triazoles is described. The molecular structure of new derivatives has been established by 1H NMR spectra and X-ray crystallographic analysis. When tested in solid agar cultures the azole derivatives showed from moderate to potent in vitro antifungal activity against Candida albicans and Candida spp.

Research on antibacterial and antifungal agents. XI: Synthesis and antimicrobial activity of N-heteroaryl benzylamines and their Schiff bases

Summary The synthesis and antimicrobial activity of new N -heteroaryl benzylamines and their Schiff bases are reported. Antifungal data were compared with those obtained with miconazole, ketoconazole, enilconazole and imazalil sulfate, which showed that some of the tested compounds possessed moderate activity against strains of Candida albicans , Candida sp and good activity against isolates of plant pathogenic fungi. In contrast the synthesized compounds showed poor antibacterial activity, except for 3j which exhibited a better activity than nalidixic acid used as positive control. The results obtained are discussed on the basis of structure-activity relationships.

Increased microbicidal activity of green tea (Camellia sinensis) in combination with butylated hydroxyanisole.

Abstract We have demonstrated that green tea (Camellia sinensis) shows increased antimicrobial activity against bacteria and fungi when used in combination with butylated hydroxyanisole (BHA). Glycolic extract taken from green tea showed only limited activity against Streptococcus mutans and no activity against Candida albicans and certain strains of Escherichia coli. BHA, at non inhibitory concentrations, increased the microbicidal activity of green tea against 1010 S. mutans (p<0.01), non-susceptible E. coli (p<0.01) and C. albicans (p<0.01). Green tea in combination with BHA reduced the hydrophobicity of S. mutans (p<0.01) and greatly inhibited (p<0.001) the formation of hyphae in C. albicans. The increased antimicrobial activity of green tea is related to an impairment of the barrier function in microorganisms and a depletion of thiol groups. The increased activity of green tea as an oral antimicrobial product is discussed.

Study of Interaction Effects of Polyacrylic Acid Polymers (Carbopol 940) on Antimicrobial Activity of Methyl Parahydroxybenzoate Against Some Gram-negative, Gram-positive Bacteria and Yeast

Cosmetic or pharmaceutical formulations containing hydrophilic polymers of natural or synthetic origin, may be more exposed to successful microbial contamination because of a polymer‐preservative interaction. The experimental data reported in this paper relate to the possible interference of Carbopol 940 with methyl parahydroxybenzoate.

Research on antibacterial and antifungal agents. X. Synthesis and antimicrobial activities of 1-phenyl-2-(1H-azol-1-yl) ethane derivatives. Anticonvulsant activity of 1-(4-methylphenyl)-2-(1H-imidazol-1-yl) ethanol

Abstract The synthesis and antimicrobial activity of new phenylazolylethane derivatives are reported. Antimicrobial data in comparison with those obtained with miconazole, fluconazole, enilconazole, imazalil sulfate, pipemidic acid and minocycline showed that tested compounds generally possessed poor or weak activity. Toxicity and anticonvulsant activity of 1-(4-methylphenyl)-2-(1H-imidazol-1-yl)ethanol and structural likeness to Denzimol were also tested. The obtained results showed interesting anticonvulsant activity but only on the supraspinal region.

Antifungal agents. 5. Chloro and amino derivatives of 1,2-diaryl-1-(1H-imidazol-1-yl)ethane with potent antifungal activities

Abstract Various derivatives of 1,2-diaryl-1-(1H-imidazol-1-yl)ethane have been synthesized and tested against Candida albicans and Candida spp. In vitro essays showed chloro and amino derivatives to be as active as miconazole and bifonazole and more potent than ketoconazole. Structure-activity relationships of the new imidazole antifungal agents are discussed.

Investigations of the activity by contact of miconazole sulfosalicylate.

The in-vitro antimicrobial activity of miconazole sulfosalicylate (M.SSA) has been investigated on mycetes (Candida albicans, Cryptococcus neoformans, Aspergillus niger, Trichophyton mentagrophytes), Gram-positive bacteria (Staphylococcus aureus, Streptococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Proteus vulgaris) in comparison with miconazole nitrate (M.NIT). The results showed M.SSA has a greater activity than M.NIT, particularly on mycetes and Gram-negative bacteria. The study of activity by contact with M.SSA showed some characteristics of this sulfosalicylate imidazole, such as the lack of a latency time, an antimicrobic action related directly to the concentration, the limited influence of pH and ionic strength of medium used. The greater activity by contact of M.SSA than M.NIT could be related to its higher lipophilia (due also to the lipophilic characteristics of SSA) and, therefore, to increased interaction with the cell membrane.

Increase of activity of tioconazole against resistant microorganisms by the addition of butylated hydroxyanisole

Tioconazole (TCZ) killed resistant Candida albicans in less than 3 min, after the addition of butylated hydroxyanisole (BHA), a phenolic antioxidant, at subinhibitory concentrations. The bactericidal activity was also rapid against resistant Escherichia coli. BHA increased the TCZ activity in RPMI 1640 medium 18 times against ten strains of resistant C. albicans as judged by MIC and increased the activity 43 times against ten resistant E. coli strains. BHA at subinhibitory concentrations promoted the reduction of C. albicans virulence by reducing 180 times the hyphal cells of TCZ and decreasing hydrophobicity. The synergy could be due to changes in cellular permeability because of increased leakage of cellular enzymes.

Research on anti-bacterial and anti-fungal agents II. Synthesis and anti-fungal activity of new(1H-imidazol-1-ylmethyl)-benzenamine derivatives

Abstract The synthesis and in vivo and in vitro anti-fungal activities of new (1H-imidazol-1-ylmethyl)benzenamine derivatives are reported. Anti-microbial data in comparison with miconazole show that many compounds exhibit an interesting anti-mycotic activity.

Tetracycline in combination with sodium dioctylsulfosuccinate show increased antimicrobial activity in resistant microorganisms

Abstract We present evidence that sodium dioctylsulfosuccinate, at non inhibitory concentrations (1000 mg/L), is able to increase the antimicrobial activity of tetracycline in non susceptible bacterial and fungal strains. In culture inhibition tests, pretreatment with sodium dioctylsulfosuccinate caused a 52-fold decrease in the geometric mean MIC to tetracycline in 10 Candida albicans strains (p<0.01), a 165-fold decrease in the geometric mean MIC to tetracycline in 10 E. coli strains (p<0.001) and a significant decrease in the mean MIC of 3 strains of Candida krusei and Candida glabrata. In microbicidal tests, tetracycline in association with sodium dioctylsulfosuccinate killed 104 cfu tetracycline-resistant Candida albicans in 15 min and 104 CFU resistant E. coli in 3 min (p<0.001). Furthermore, in the Nacetyl- D-glucosamine test to calculate the number of hyphal cells, a combination of tetracycline (50 mg/L) (non inhibitory concentrations) plus sodium dioctylsulfosuccinate (25 mg/L) caused a 50-fold increase in the inhibition of hyphal cells in C. albicans (p<0.001); C. albicans cells treated with tetracycline plus sodium dioctylsolfosuccinate annulled the cell surface hydrophobicity (p<0.001). This increase in antimicrobial activity may be attributed to impairment and alteration of the membrane barrier within the microorganisms and a depletion of the thiol groups (p<0.001) critical to their efficiency.