Antibacterial effect of substituted 4-quinazolylhydrazines and their arylhydrazones determined by a modified microdilution method

Eight 4-quinazolylhydrazines and eleven their arylhydrazones have been tested for antibacterial effects and for structure-activity relationships by a modifed microdilution method. The derivative 6-chloro-2-morpholino-4-quinazolyl-5′-nitro-2′-furylhydrazone had the highest antibacterial effect, the MIC values being 100 mg/L forE. fœcalis, 250 mg/L forS. aureus, 200 mg/L forP. aeruginosa and 350 mg/L forE. coli. The most effective derivatives were those with the benzene ring substituted with chlorine or methyl group in position 6 or 8 and with pyrimidine ring substituted with a secondary amine in position 2. The modified microdilution method did not give rise to any statistically significant deviations in the MIC values for ampicillin in comparison with reported reference collection values. Dedicated to Professor Vladimír Betina, DSc. on the occasion of his 65th birthday     

Antibacterial effect of some substituted tricyclic quinazolines and their synthetic precursors

Eleven substituted tricyclic quinazolines and their synthetic precursors were tested for antibacterial effects. 3-Chloromethylcarbonyl-2-methylquinazolin-4-thione and 5-phenyl-2,3-dihydro-1,2,4-triazolo[4,3-c]quinazolin-3-one had the highest antibacterial effect againstBacillus subtilis, the MIC values being 50 mg/L. Two tested derivatives were more active againstPseudomonas aeruginosa than ampicillin, the IC₅₀ values being 80 and 100 mg/L. The most effective derivatives contained in the structure generally pharmacologically active chromophores—methyl group in position 2 and a chloromethyl configuration on the carbonyl group in position 3.     

Antibacterial and mutagenic activities of new isothiocyanate derivatives

Nine newly synthetized isothiocyanate derivatives were demonstrated to posses antibacterial and genotoxic activitiesin vitro. 4-Hydroxybutyl isothiocyanate exhibited a broad antibacterial effect, with MIC values of 762 μmol/L forStaphylococcus aureus andEscherichia coli. Ethyl 4-methylsulfoxidobutanoate had the highest antibacterial activity in Gram-positive bacteria, the MIC value being 425 μmol/L forS. aureus. The highest tested concentrations of ethyl 4-isothiocyanatobutanoate and 4-hydroxybutyl isothiocyanate produced a bacteriocidal effect in Gram-positive bacteria. The compounds showed no mutagenic effects onSalmonella typhimurium tester strains TA 98 and TA 100, either in the absence or in the presence of a metabolically active microsomal S9 fraction from rat liver using standard Ames test.     

Antibacterial effects of some 1-substituted 1,2,4-triazoles

Seventeen synthetic 1-substituted 1,2,4-triazoles exerted a significant effect on the bacteriaB. subtilis, S. aureus, E. coli andP. aeruginosa. The least sensitive to the effects of the triazoles wasS. aureus. With all triazole derivatives and their combinations,B. subtilis andP. aeruginosa exhibited IC₅₀ and MIC values several times higher than with ampicillin. The most effective triazoles have a N-phenyl ring or benzimidinoyl ring substituted with one or several chlorine atoms. The highest tested concentration of the three most effective triazoles influenced the specific growth rate.     

Structure-activity relationships of some 4-quinazolylthiosemicarbazides and their triazolo derivatives

Eigh 4-quinazolylthiosemicarbazides and nine of their structural analogues have been tested for antibacterial effects and for structure activity relationships. 9-Chloro-5-morpholino-1,2,4-triazolo[4,3-c]quinazoline-3-thione has demonstrated the hightest antibacterial effect (MIC of 1 mg/L forE. coli andP. mirabilis and <1 mg/L forS. aureus andB. subtilis). The most effective derivatives have the carbon aromatic ring substituted with chlorine and the pyrimidine ring with morpholine or with secondary amine group.     

Dryoptkirbioside,A New Fructofuranoside Glycerol,and Other Constituents from Dryopteris kirbi Hook et Grav Rhizomes

A new fructofuranoside glycerol, dryoptkirbioside ( 1 ), along with thirteen known compounds ( 2 - 14 ), was isolated from the MeOH extract of Dryopteris kirbi rhizomes by silica gel column chromatography, Sephadex LH-20 column chromatography, and semipreparative HPLC. The structure of the new compound was determined by analyses of its spectroscopic data including nuclear magnetic resonance (NMR), and high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) and chemical conversions. The hexane-soluble portion and the EAF_A fraction showed strong activities against lung (A549), breast (MCF-7), and cervical (HeLa) human cancer cell lines (IC₅₀ values ranging from 4.0 to 8.8 μg/mL). Aspidinol P ( 5 ) and aspidinol B ( 6 ) exhibited moderate to low cytotoxicity on the three cell lines (IC₅₀ values ranging from 20.4 to 58.7 μM). The MeOH extract and hexane-soluble portion had excellent activities against Staphylococcus aureus and Bacillus subtilis (MICs 11.7 and 23.4 μg/mL), whereas the AcOEt- and BuOH-soluble portions were significantly active on S. aureus (MICs 46.9 and 93.8 μg/mL). The main fractions EAF_B, EAF_C and nBF_B displayed excellent activity against S. aureus (MICs 11.7 and 23.4 μg/mL). Aspidinol B ( 6 ) had significant activity, while aspidinol P ( 5 ) was moderately active against S. aureus and B. subtilis (MICs 42.0 and 89.5 μM).     

Individual- and population-level effects of antibiotics on the rotifers, <Emphasis Type="Italic">Brachionus calyciflorus</Emphasis> and <Emphasis Type="Italic">B. plicatilis</Emphasis>

The toxicity of three common antibiotics (streptomycin sulfate, tetracycline hydrochloride, and tylosin tartrate) to the freshwater rotifer Brachionus calyciflorus and brackish-water rotifer B. plicatilis was investigated using full-lifespan exposure durations. Effects of each antibiotic on lifespan, lifetime reproduction, and Malthusian parameter were assessed at seven nominal concentrations (ranging from 5.6 mg l⁻¹ to 2,000 mg l⁻¹) and a negative control. Lowest Observed Effect Concentrations (LOECs) were determined for reproduction and lifespan, while 1%, 10%, 25%, and 50% Inhibitory Concentrations (IC₁, IC₁₀, IC₂₅, IC₅₀) and 95% confidence intervals were estimated for all three endpoints. LOECs ranged from 5.6 mg l⁻¹ to 90 mg l⁻¹, with all LOECs less than 90 mg l⁻¹ occurring in B. calyciflorus. The lowest IC1 concentrations were 3.91 mg l⁻¹ for the effect of tetracycline on lifetime reproduction in B. calyciflorus and 4.06 mg l⁻¹ for the effect of tylosin on lifetime reproduction in B. plicatilis. Overall, lifetime reproduction was the most sensitive endpoint and the Malthusian parameter was the least sensitive. IC₁ values for lifetime reproduction were roughly one to two orders of magnitude lower than the corresponding IC₅₀ values. Guest editors: S. S. S. Sarma, R. D. Gulati, R. L. Wallace, S. Nandini, H. J. Dumont and R. Rico-Martínez Advances in Rotifer Research     

In Vitro Antibacterial Activity of 4-Phenyl-1-(2-phenyl-allyl)pyridinium bromide: A Novel Class of Pyridinium Based Antibacterial Compounds

The continuing increase in the incidence of multi drug resistant pathogenic bacteria and shortage of new antimicrobial agents are the prime driver in efforts to identify the novel antimicrobial classes. In vitro antibacterial activity of 4-phenyl-1-(2-phenylallyl) pyridinium bromide was tested against Gram positive Staphylococcus aureus, Streptococcus species, Bacillus subtilis, and Gram negative Klebsiella aerogenes and Escherichia coli using disk diffusion method. Among them S. aureus showed strong antibacterial activity (21.99 ± 0.03 mm) while E. coli showed very little activity (8.97 ± 0.06 mm) towards the compound. The MIC of 4-phenyl-1-(2-phenyl-allyl)-pyridinium bromide for 90% S. aureus was ≤20 μg/ml and was compared with phenoxymethylpenicillin, cloxacillin, erythromycin and vancomycin. When 4-phenyl-1-(2-phenyl-allyl)pyridinium bromide showed MIC at ≤20 μg/ml, all others showed MIC at ≤100 μg/ml. Strong antibacterial activity of 4-phenyl-1-(2-phenyl-allyl)pyridinium bromide against S. aureus indicates that there is a possibility to use it as an effective antibacterial agent.     

Linezolid Is a Specific Inhibitor of 50S Ribosomal Subunit Formation in Staphylococcus aureus Cells

Linezolid is an oxazolidinone compound that has been shown to have impressive antimicrobial activity against a number of Gram-positive bacteria. It inhibits an initiation step of protein synthesis, and its binding site has been shown to be on the 50S ribosomal subunit. Linezolid was tested to see whether would interfere with the formation of the 50S subunit in Staphylococcus aureus cells, since a number of other 50S-specific antibiotics have this second inhibitory function. Linezolid inhibited protein synthesis in S. aureus cells with an IC₅₀ of 0.3 μg/ml. A concentration-dependent decline in cell number with an increase in generation time was found. Pulse-chase labeling studies revealed a specific inhibitory effect on 50S particle formation, with no effect on 30S subunit assembly. The compound inhibited 50S synthesis with an IC₅₀ of 0.6 μg/ ml, indicating an equivalent effect on translation and particle assembly. A postantibiotic effect of 1 h was found when cells were initially treated with the drug at 2 μg/ ml. 50S particle numbers recovered more rapidly than translational capacity, consistent with the increase in viable cell numbers. The inhibitory activities of this novel antimicrobial agent in cells are discussed. Received: 28 June 2001 / Accepted: 27 August 2001     

Preparation of Some New Pyrazolo[1,5-a]pyrimidines and Evaluation of Their Antioxidant,Antibacterial (MIC and ZOI) Activities,and Cytotoxic Effect on MCF-7 Cell Lines

This study aims to synthesize some novel pyrazolo[1,5-a]pyrimidine derivatives, and investigate their biological activities. These compounds exhibited good to high antioxidant activities [2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capabilities]. Among them, Ethyl 5-(2-ethoxy-2-oxoethyl)-7-hydroxy-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxylate ( 3h ) showed the highest antioxidant activity [Half-maximal Inhibitory Concentration (IC₅₀)=15.34 μM] compared to ascorbic acid (IC₅₀=13.53 μM) as a standard compound. Their antibacterial activities were investigated against two Gram-positive bacteria (Bacillus subtilis, and Staphylococcus aureus) and two Gram-negative bacteria (Pseudomonas aeruginosa, and Escherichia coli). The results showed that Ethyl 7-hydroxy-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate ( 3i ) has the best antibacterial activity against Gram-positive B. subtilis [Zone of Inhibition (ZOI)=23.0±1.4 mm, Minimum Inhibitory Concentration (MIC)=312 μM]. Also, the cytotoxicity of these compounds was assessed against breast cancer cell lines [human breast adenocarcinoma (MCF-7)], which 7-Hydroxy-2-methyl-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ( 3f ) displayed the most cytotoxicity (IC₅₀=55.97 μg/mL), in contrast with Lapatinib (IC₅₀=79.38 μg/mL) as a known drug.     

Interaction of benzo[c]phenanthridine and protoberberine alkaloids with animal and yeast cells

We compared the effects of four quaternary benzo[c]phenanthridine alkaloids – chelerythrine, chelilutine, sanguinarine, and sanguilutine – and two quaternary protoberberine alkaloids – berberine and coptisine – on the human cell line HeLa (cervix carcinoma cells) and the yeastsSaccharomyces cerevisiae andSchizosaccharomyces japonicus var. versatilis. The ability of alkaloids to display primary fluorescence, allowed us to record their dynamics and localization in cells. Cytotoxic, anti-microtubular, and anti-actin effects in living cells were studied. In the yeasts, neither microtubules nor cell growth was seriously affected even at the alkaloid concentration of 100 μg/ml. The HeLa cells, however, responded to the toxic effect of alkaloids at concentrations ranging from 1 to 50 μg/ml. IC₅₀ values for individual alkaloids were: sanguinarine IC₅₀ = 0.8 μg/ml, sanguilutine IC₅₀ = 8.3 μg/ml, chelerythrine IC₅₀ = 6.2 μg/ml, chelilutine IC₅₀ = 5.2 μg/ml, coptisine IC₅₀ = 2.6 μg/ml and berberine IC₅₀ >10.0 μg/ml. In living cells, sanguinarine produced a decrease in microtubule numbers, particularly at the cell periphery, at a concentration of 0.1 μg/ml. The other alkaloids showed a similar effect but at higher concentrations (5–50 μg/ml). The strongest effects of sanguinarine were explained as a consequence of its easy penetration through the cell membrane owing to nonpolar pseudobase formation and to a high degree of molecular planarity. This revised version was published online in July 2006 with corrections to the Cover Date.     

Inhibition of Sortase,a Bacterial Surface Protein Anchoring Transpeptidase,by β-Sitosterol-3-O-glucopyranoside from Fritillaria verticillata

A glucosylsterol, β-sitosterol-3-O-glucopyranoside, has been isolated as an active principle with sortase inhibitory effect from the bulbs of Fritillaria verticillata by bioassay-guided chromatographic fractionation. The isolate was a potent inhibitor of sortase, with an IC₅₀ value of 18.3 μg/ml and had antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Micrococcus leuteus with MIC values of 50, 200, and 400 μg/ml, respectively, indicating that this compound is a possible candidate for the development of a bacterial sortase inhibitor. In addition, sitosterol was found to be inactive upon sortase and bacterial cell growth. These results suggest that the inhibitory potency of β-sitosterol-3-O-glucopyranoside is sensitively dependent upon the glucopyranoside side chain moiety.     

Isolation and identification of antimicrobial agent-producing bacterium from <Emphasis Type="Italic">Taxus baccata</Emphasis> rhizosphere antagonistic against clinically significant microbes

A bacterium identified as Pseudomonas fluorescence was isolated from Taxus baccata rhizosphere. Ethyl acetate extract from its culture filtrate yielded an active antimicrobial compound that was purified by TLC. The active metabolites were resolved by column chromatography on silica gel (60–120 mesh). The compound was further characterized on the basis of spectral data (UV, IR and ¹HNMR), which indicated the presence of an aromatic ring and phenolic functionality. The compound showed significant antimicrobial activity against two-gram positive bacteria (B. subtilis and S. aureus), four-gram negative bacteria (E. coli, K. pneumoniae, S. flexneri and P. aeruginosa), and one pathogenic fungus (Candida albicans). The minimum inhibitory concentration (MIC) of the compound ranged between 75μg to 250 μg/ml.     

Tertiary structure-related activity of tick defensin (persulcatusin) in the taiga tick, <Emphasis Type="Italic">Ixodes persulcatus</Emphasis>

Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates constituting the front line of host innate immunity. To examine the importance of the tertiary structure of tick defensin in its antimicrobial activity, we synthesized two types of the peptides with tertiary structure or primary one on basis of the information of the sequence in the defensin originated from the taiga tick, Ixodes persulcatus. Chemically synthesized peptides were used to investigate the activity spectrum against Staphylococcus aureus, Borrelia garinii and flora-associated bacteria. Both synthetic peptides showed antimicrobial activity against S. aureus in short-time killing within 1 h, but they do not show the activity against B. garinii, Stenotrophomonas maltophila and Bacillus spp., which were frequently isolated from the midgut of I. persulcatus. The teriary structure brought more potent activity to S. aureus than primary one in short-time killing. We also examined its antimicrobial activity by evaluation of growth inhibition in the presence of the synthetic peptides. Minimum inhibitory concentration (MIC) was ranged from 1.2 to 5.0 μg/ml in tertiary peptide and from 10 to 40 μg/ml in primary peptide, when 10 strains of S. aureus were used. From the curve of cumulative inhibition rates, MIC50 (MIC which half of the strains showed) to S. aureus is about 1.2 μg/ml in the peptide with tertiary structure and about 10 μg/ml in the linear one. Corynebacterium renale is 10 times or more sensitive to tertiary peptide than primary one. In conclusion, the presence of 3 disulfide bridges, which stabilize the molecule and maintain the tertiary structure, is considered to have an effect on their antimicrobial activities against Gram-positive bacteria such as S. aureus.     

TAN-1057A: A Translational Inhibitor with a Specific Inhibitory Effect on 50S Ribosomal Subunit Formation

The inhibitory activities of a novel antibiotic compound have been investigated. A synthetic version of the natural product TAN-1057A was examined for its effects on translation and ribosomal subunit formation. The antibiotic at 6 μg/ml reduced the growth rate of wild-type Staphylococcus aureus cells by 50%. The IC₅₀ for inhibition of protein synthesis in these cells was 4.5 μg/ml. Pulse and chase labeling kinetics showed a strong inhibitory effect on 50S ribosomal subunit formation as well. The IC₅₀ for this process was 9 μg/ml, indicating an equivalent inhibitory effect of the antibiotic on translation and 50S synthesis. The post-antibiotic effect of the drug was investigated. Protein synthesis resumed rapidly after removal of the drug from cells, but full recovery of the normal 50S subunit complement in treated cells required 1.5 h. The dual inhibitory effects of this compound are compared with other antimicrobial agents having similar effects on cell growth. Received: 27 December 2000 / Accepted: 22 March 2001     

Synthesis,Characterization, Antimicrobial and Antimalarial Activities of Azines Based Schiff Bases and their Pd(II) Complexes

Herein, we report synthesis, characterization, antimicrobial and antimalarial activities of azines Schiff base ligands (L¹−L⁴) and their palladium (II) complexes ( C¹−C⁴ ) of [Pd(L)(OAc)₂] type. The azine ligands (L¹−L⁴) were prepared by condensation of carbonyl compounds with hydrazine hydrate and their complexes by the reaction of palladium acetate with L¹−L⁴ ligands in 1 : 1 molar ratio. The prepared ligands and their complexes were characterized by spectral characterization using ¹H &¹³C-NMR, FT-IR and mass spectral studies, which revealed that the ligands coordinates via azomethine nitrogen and heteroatom or aryl carbon with palladium. Moreover, Schiff bases and their palladium (II) complexes have been screened for their antibacterial (S. aureus, B. subtillis, and S. typhi, P. aeruginosa), antifungal (C. albicans, A. niger, and A. clavatus) and antimalarial (P. falciparum) activities. The Schiff base L⁴ showed good results for antibacterial against S. aureus (MIC, 50 μg/mL) and antimalarial against P. falciparum (IC₅₀, 0.83 μg/mL). The complex C¹ showed best antibacterial activity (MIC, 62.5 μg/mL) against S. typhi and the complex C⁴ exhibited remarkable antimalarial activity (IC₅₀, 0.42 μg/mL) among the tested compounds. Thus, azines based ligands and their Pd complexes can be good antimicrobial and antimalarial agents if explored further.     

Chemical composition and antimicrobial,antioxidant, and anti-inflammatory activities of Lepidium sativum seed oil

Lepidium sativum (garden cress) seed oil was examined for its antimicrobial, antioxidant, and anti-inflammatory activities. The oil was obtained by hydrodistillation, where gas chromatography coupled with mass spectrometry that utilized to study its chemical composition. Microdilution method was used to test the antimicrobial effect of oil against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enterica, Klebsiella pneumoniae, and Candida albicans. The antioxidant activity was assessed by radical scavenging activity assay using 2,2-diphenyl-1-picrylhydrazyl radical. The major constituents found in the oil were 7,10-hexadecadienoic acid, 11-octadecenoic acid, 7,10,13-hexadecatrienoic acid, and behenic acid. The minimum inhibitory concentration (MIC) against all pathogens was 47.5 mg/ml, except for Salmonella enterica, which showed MIC of 90 mg/ml. The oil demonstrated antioxidant activity in a dose dependent pattern, with a half maximal inhibitory concentration (IC₅₀) value of 40 mg/ml, and exerted anti-inflammatory activity, wherein 21% protection was shown at a concentration of 300 μg/ml. Thus, L. sativum seed oil shows antimicrobial, antioxidant, and anti-inflammatory properties.     

Comparative in vitro activity of moxalactam (LY127935), other beta-lactam antibiotics,and aminoglycosides

Moxalactam (LY127935), a novel beta-lactam antibiotic, was compared with semisynthetic penicillins, cephalosporins, and aminoglycosides by the agar dilution method against 5,317 recent clinical isolates of facultative and anaerobic bactria. At 0.5 μg/ml, moxalactam inhibited 90% of all Gram-negative bacilli tested except forPseudomonas aeruginosa (81% inhibited by 32 μg/ml) andAcinetobacter calcoaceticus (88% inhibited by 32 μg/ml). More than 90% ofBacteroides fragilis andStaphylococcus aureus were inhibited by 4 μg/ml and 8 μg/ml, respectively. Moxalactam was at least 16-fold more active by weight than cephalothin, cefamandole, and cefoxitin forEscherichia coli, Klebsiella pneumoniae, andEnterobacter species, and 2- to 4-fold more active than cefoxitin forB. fragilis. Moxalactam was 4-fold less active than cefamandole and cephalothin forS. aureus and 2- to 4-fold less active than piperacillin forP. aeruginosa. Moxalactam was as active or more active than the aminoglycosides for all facultative Gram-negative bacilli except forP. aeruginosa. Moxalactam was inhibitory (minimal inhibitory concentration <16 μg/ml) for 20/27 gentamicin-resistant isolates and 8/13 amikacin-resistant organisms. Moxalactam’s in vitro activity against Gram-negative bacilli is markedly superior to presently available cephalosporins and, except forP. aeruginosa, is comparable to the aminoglycosides.     

Identification and Characterization of Novel Lipophilic Antimicrobial Peptides Derived from Naturally Occurring Proteins

Microbes are increasingly developing defensive mechanisms against known drugs via mutations. There are signs of emergence of superbugs immune to most known antibiotics available. The need for a new class of drugs to counteract this problem is of paramount importance for continued general well being of mankind. A new class of drugs, antimicrobial peptides, has not been fully exploited primarily due to high cytotoxicity, poor lipophilicity preventing systemic distribution and stability. We have synthesised 9-amino acid residue cationic peptides RH01 and RH02 lipidated with myristoyl and octyl groups respectively. These peptides exhibited potent antimicrobial activity and low cytotoxicity. The lipopeptide RH01 has antimicrobial activity against a broad range of microorganisms including bacteria, yeast and filamentous fungi with greatest activity toward Gram-positive bacteria, including S. aureus MRSA stain, MIC’s ranging between 2–8 μM. The MIC for Gram-negative bacteria was higher ranging from between 30–250 μM. RH01 also had antimicrobial activity towards fungi showing good activity against the pathogenic yeast Candida albicans but was less active towards the filamentous fungi Aspergillus niger. The antimicrobial activity of RH01 as a measure of Ki₍₅₀₎ for E. coli and S. aureus was 35–60 μM and 3–7 μM, respectively. In-house data showed the compound is bactericidal even at higher bacteria concentration. The octylated lipopeptide RH02 has similar activities towards S. aureus (3.3 μM) and E coli (53.3 μM) as the myristolated RH01. There was no haemolytic activity of the lipopeptide RH01 towards human blood. Acute intravenous toxicity study in mice showed that both RH01 and RH02 induced no macroscopic abnormalities at their highest non-lethal dose of 75 mg/kg and 150 mg/kg bodyweight, respectively.Australian Peptide Conference Issue.     

Inhibition of yeast-mycelium transformation by 2-alkylthio-6-amino-and 2-alkylthio-6-formamidobenzothiazoles and theirin vitro antifungal activity

The antifungal effect of 2-alkylthio-6-amino-and 2-alkylthio-6-formamidobenzothiazoles (22 derivatives in all) onAspergillus niger and variousCandida yeasts was tested. No significant effect was observed withA. niger. With the pathogenic yeast speciesC. albicans andC. guilliermondii, the most efficient derivatives (6-formamido-2-propylthio-, 6-formamido-2-butylthio-, 6-formamido-2-pentylthio-and 6-formamido-2-isopentylthiobenzothiazole) exhibited ED₅₀ values in the range from 2.2 to 21 mg/L and were thus 3–35 times more efficient than 2-mercaptobenzothiazole (Dermacid) that is normally used. 6-Amino-2-pentylthiobenzothiazole was found to be an efficient specific inhibitor of the transformation of the yeast form ofC. albicans to its mycelial one, IC_95(M) being 10 mg/L, which was a concentration 25 times lower than MIC_Y+M.