Antimicrobial activity of a series of thiosemicarbazones and their Zn(II) and Pd(II) complexes.

Thirty-four thiosemicarbazones and S-alkyl thiosemicarbazones, and some of their Zn(II) and Pd(II) complexes were obtained and purified to investigate antimicrobial activity. MIC values of the compounds were determined by the disc diffusion method against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Staphylococcus aureus, S. epidermidis, and Candida albicans. The thiosemicarbazones show antibacterial and antifungal effects in free ligand and metal-complex form. Picolinaldehyde-S-methyl- and -S-benzylthiosemicarbazones did not affect the tested microorganisms but their Zn(II) complexes showed selective activity. The antimicrobial activity is relatively high in Me2SO, but the antimicrobial potential is changed in a certain range with Me2SO, HCONMe2, EtOH and CHCl3.

Antimicrobial activity of 1,2-bis-[2-(5-R)-1H-benzimidazolyl]- 1,2-ethanediols, 1,4-bis-[2-(5-R)-1H-benzimidazolyl]- 1,2,3,4-butanetetraols and their FeIII, CuII, and AgI complexes.

1,2-Bis-[2-(5-H/Me/Cl/NO2)-1H-benzimidazolyl]-1,2-ethanediols (L1-L4), 1,4-Bis-[2-(5-H/Me/Cl)-1H-benzimidazolyl]-1,2,3,4-butanetetraols (L5-L7) and their complexes with FeCl3, CuCl2, and AgNO3 were synthesized; antibacterial activity of the compounds was determined toward Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Proteus mirabilis, and antifungal activity against Candida albicans. The AgI complexes have considerable activity toward the microorganisms. Some AgI complexes show higher activity toward S. epidermidis than AgNO3 and cefuroxime. Cu(L3)Cl2 and Fe(L3)Cl3 show an antifungal effect on C. albicans but L3 itself has no activity.

Antimicrobial activity of ZnII, CdII, and HgII complexes of 1,2-bis-[2-(5-R)-1H-benzimidazolyl]-1,2-ethanediols and 1,4-bis-[2-(5-R)-1H-benzimidazolyl]-1,2,3,4-butanetetraols.

1,2-Bis-[2-(5-H/Me/Cl/NO2)-1H-benzimidazolyl]-1,2-ethanediols (L1-L4), 1,4-bis-[2-(5-H/Me/Cl)-1H-benzimidazolyl]-1,2,3,4-butanetetraols (L5-L7) and their complexes with ZnCl2, CdCl2 and HgCl2 were synthesized and antibacterial activity of the compounds was tested toward Staphylococcus aureus, S. epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Proteus mirabilis and antifungal activity against Candida albicans. HgII complexes have a considerably higher antimicrobial activity against all microorganisms. Some HgII complexes show higher antifungal activity than clotrimazole toward C. albicans. Zn2(L3)Cl4, Zn2(L4)Cl4, and Cd(L3)Cl2 were moderately effective against S. aureus and S. epidermidis; Cd(L4)Cl2 exhibited a weak activity only against S. epidermidis.

Antimicrobial activity of some 2- and 3-pyridinyl-1H-benzimidazoles and their FeIII, CuII, ZnII, and AgI complexes.

2-(2-Pyridinyl)- (LI), 2-(6-methyl-2-pyridinyl)- (LII), 2-(6-methyl-2-pyridinyl)-5-methyl-(LIII), 2-(3-pyridinyl)- (LIV), 2-(3-pyridinyl)-5-methyl-1H-benzimidazoles (LV) and their complexes with Fe(NO3)3, Cu(NO3)2, Zn(NO3)2, and AgNO3 were synthesized and antibacterial activity of the compounds was tested toward Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, Proteus mirabilis and antifungal activity against Candida albicans. The methyl groups of LIII increase the antimicrobial activity. The AgI complexes have considerable activity toward the microorganisms. Some ZnII complexes show an antimicrobial effect against S. aureus and S. flexneri, although the ligands themselves have no effect. CuII complexes have a considerable antibacterial effect to S. aureus and S. epidermidis.

Antimicrobial activity of FeIII, CuII, AgI, ZnII and HgII complexes of 2-(2-hydroxy-5-bromo/nitro-phenyl)-1H- and 2-(2-hydroxyphenyl)-5-methyl/chloro/nitro-1H-benzimidazoles.

Antimicrobial activity of 2-(2-hydroxyphenyl)-5-R5-1H-benzimidazoles, 2-(2-hydroxy-5-R5'-phenyl)-1H-benzimidazoles and their FeIII, CuII, AgI, ZnII and HgII nitrate complexes was tested toward Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, and Proteus mirabilis. Antifungal activity was tested against Candida albicans. Benzimidazole benzene ring substituents increase the antimicrobial activity, phenol ring substituents decrease it. The ligands show an antibacterial effect against only S. aureus whereas AgI and HgII complexes of the ligands have a higher activity with respect to the other complexes to all the bacteria. On the other hand, FeIII complexes show a considerable activity against S. aureus and S. epidermidis.

Synthesis of Mannich bases of some 2,5-disubstituted 4-thiazolidinones and evaluation of their antimicrobial activities.

5-Phenyl/methyl-5-morpholinomethyl/pyrrolidinomethyl-2-(5- aryl-1,3,4-oxadiazol-2-yl)imino]-4-thiazolidinones (5a-m) were synthesized by the reaction of 5-phenyl/methyl-2-[(5-aryl-1,3,4-oxadiazol -2-yl)imino]-4-thiazolidinones (4a-j) with formaldehyde and morpholine or pyrrolidine. The structures of the compounds were determined by analytical and spectral (IR, 1H-NMR, EIMS) methods. The antibacterial activities of the novel compounds against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri and Proteus mirabilis and antifungal activity against Candida albicans ATCC 10231 were tested using the disk diffusion method. Compounds 5a, 5b, 5c, 5e, 5g, and 5h were found to be active against S. aureus ATCC 6538 (MIC: 312.5; 39; 19.5; 39; 156; and 78 micrograms/mL respectively) and compounds 5c and 5h against S. flexneri (MIC: both 312.5 micrograms/mL). The minimal inhibitory concentrations of these compounds were determined using the micro dilution method.

Synthesis and antimicrobial activity of some 1,2,4-triazole-3-mercaptoacetic acid derivatives.

Ethyl 5-(2-furyl)-4-ethyl-1,2,4-triazole-3-mercaptoacetate (2), 5-(2-furyl)-4-ethyl-1,2,4-triazole-3-mercaptoacetic acid hydrazide (3) and a series of new N-alkylidene/arylidene-5-(2-furyl)-4-ethyl-1,2,4-triazole-3-mercaptoacetic acid hydrazides (4a-f) were synthesized and evaluated for in vitro antibacterial activity against Staphylococcus aureus ATCC 6538. Staphylococcus epidermidis ATCC 12228, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Escherichia coli ATCC 8739, Shigella flexneri, Salmonella typhi, Proteus mirabilis and antifungal activity against Candida albicans ATCC 10231 using the disk diffusion and microdilution methods. Compound 4f showed antibacterial activity against some bacteria. The in vitro antimycobacterial activity of the new compounds against Mycobacterium tuberculosis H37Rv was evaluated employing the BACTEC 460 radiometric system. The highest inhibition observed was 61% at > 6.25 microg/ml.

Synthesis and evaluation of antibacterial activity of some 2-[[alpha-(4-substituted benzoyloxy)-alpha-phenylacetyl or methylacetyl]amino]-5-(4-methoxyphenyl)- 1,3,4-oxadiazoles.

In this study, a new series of 1-[[alpha-(4-substitutedbenzoyloxy)-alpha-phenylacetyl or methylacetyl]amino]-5-(4-methoxyphenyl)-1,3,4-oxadiazoles were obtained by condensation of 2-[(alpha-chloro-alpha-phenylacetyl or alpha-bromopropionyl)amino]-5-(4-methoxyphenyl)1,3,4-oxadiazoles with sodium salts of 4-substituted benzoic acids. Structures of the compounds were assigned on the basis of spectral data (UV, IR, 1H NMR, El MS) and elemental analyses. The antibacterial activities of the novel compounds against Staphylococcus aureus ATCC 6538. Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri and Proteus mirabilis and antifungal activity against Candida albicans ATCC 10231 were tested using disk diffusion method. Compounds 4a, 4d and 4g were found to be active against S. aureus ATCC 6538 (MIC, 78, 39 and 78 microg ml(-1), respectively) and compound 4e against S. epidermidis ATCC 12228 (MIC, 156 microg ml(-1)).

Synthesis of some 4-(alkylidene/arylidene)amino-2,4-dihydro-5- (2-thienyl)-3H-1,2,4-triazole-3-thiones tested for antimicrobial activity.

A series of 4-(alkylidene/arylidene)amino-2,4-dihydro-5- (2-thienyl)-3H-1,2,4-triazole-3-thiones (2a-h) were synthesized. The structural elucidation of all the compounds was made on the basis of analytical and spectral data (IR, 1H-NMR and EIMS). All synthesized compounds were evaluated for in vitro antimicrobial activity against various bacteria and fungi. Some of the compounds demonstrated antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Trichophyton rubrum, Trichophyton mentagrophytes var. erinacei NCPF-375 and Microsporum canis (MIC 50-6.25 mg/ml). The in vitro antimycobacterial activity of the new compounds was also investigated. Some of the compounds showed varying degrees of inhibition (2-40%) against Mycobacterium tuberculosis H37Rv in the primary screen that was conducted at 12.5 mg/ml using the BACTEC 460 radiometric system.

Synthesis and antimicrobial activity of new 6-phenylimidazo[2,1-b]thiazole derivatives.

A series of new N2-substituted-6-phenylimidazo[2,1-b]thiazole-3-acetic acid hydrazides (2a-j) were synthesized and evaluated for in vitro antimicrobial activity against various bacteria and fungi. Some of the compounds showed antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Trichophyton mentagrophytes var. Erinacei NCPF-375, Trichophyton rubrum and Microsporum audounii (MIC 25-0.24 micrograms/ml). The in vitro antimycobacterial activity of the new compounds was also investigated. The compounds exhibited different degrees of inhibition (17.98%) against Mycobacterium tuberculosis H37Rv in the primary screen that was conducted at 12.5 micrograms/ml using the BACTEC 460 radiometric system.

Synthesis and antimicrobial activity of 4-carbethoxymethyl-2-[(alpha-haloacyl)amino] thiazoles and 5-nonsubstituted/substituted 2-[(4-carbethoxymethylthiazol-2-yl)imino]-4-thiazolidinones.

4-Carbethoxymethyl-2-[(chloroacetyl/alpha-chloropropionyl/al pha- bromobutyryl/alpha-chloro-(alpha-phenylacetyl)amino]thiazoles (I-IV) were synthesized by reacting 4-carbethoxymethyl-2-aminothiazole with chloroacetyl chloride, alpha-chloropropionyl chloride, alpha-bromobutyryl bromide and alpha-chloro-alpha-phenylacetyl chloride, respectively. Furthermore, I-IV were refluxed with ammonium thiocyanate to give 2-[(4-carbethoxymethylthiazol-2-yl)imino]-4-thiazolidinones (V-VIII). V was refluxed with various aromatic aldehydes to give 5-arylidene-2-[(4-carbethoxymethylthiazol-2-yl)imino]-4-t hiazolidinones (IX-XIV). The structures of synthesized compounds were confirmed by elemental analyses, hydrolysis, UV, IR, 1H-NMR and EI mass spectral data. The antimicrobial activities of the compounds were assessed by microbroth dilution technique using Mueller-Hinton broth and Mueller-Hinton Agar. In this study, Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis and Candida albicans ATCC 10231 were used as test microorganisms. Among the tested compounds, XI and XIV showed activity against S. aureus (MIC: 78 micrograms/ml, 1.6 micrograms/ml), whereas compound V had an activity against S. flexneri (MIC: 39 micrograms/ml) and compound I against C. albicans (MIC: 125 (micrograms/ml). Compounds I, IV-XIV were also evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv using the BACTEC 460 radiometric system and BACTEC 12B medium. Only compounds I and XIV showed 86% and 67% inhibition in the primary screen.

Synthesis, Characterization and Antimicrobial Activity of d Metal Complexes of some 2-Substituted-1H-Benzimidazoles.

The metal complexes of nine 2-substituted-1H-benzimidazoles (I-IX) with Ni(II), Pd(II), Cu(II), Ag(I), Zn(II) salts were synthesized. The compounds were characterized by melting point, analytical data, IR spectroscopy and magnetic susceptibility. The antimicrobial activity of the compounds was determined by the disk diffusion method in Mueller-Hinton Agar on Staphylococcus aureusATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis, Candida albicans ATCC 10231. Cu(II)and Ag(I)complexes of II, III and IV showed considerable activity against S. aureus, S. epidermidis, Ps. aeruginosa, S. typhi, Sh. flexneri and C. albicans microorganisms, the ligands themselves having no effect.

5-Nitroimidazole derivatives as possible antibacterial and antifungal agents.

Some novel 1-[2-[[5-(2-furanyl)-4-substituted 4H-1,2,4-triazol-3-yl[thio[ethyl[-2-methyl-5-nitro-1H-imidazoles (3), 1-[3-[[5-(2-furanyl/2-thienyl)-4-substituted 4H-1,2,4-triazol-3-yl[-thio]-2-hydroxypropyl[-2-methyl-5-nitro-1H- imidazoles (5) and 1-[3-[(N,N-disubstituted thiocarbamoyl)-thio[-2-hydroxypropyl]-2-methyl-5-nitro-1H-imidazoles (7) were synthesized and evaluated for in vitro antibacterial and antifungal activity. Some of 5 were found to be effective against bacteria and fungi (minimum inhibitory concentration (MIC) 7.3-125 micrograms/ml), whereas 7 were found to be effective against fungi (MIC 3-25 micrograms/ml).

New 4-thiazoline-2-hydrazono-1H-2-indolinones as possible antimicrobial agents.

In order to test their antimicrobial activity a series of new 3-[(3-substituted-4-methyl-5-carboxy/carbetoxy-4-thiazolin-2 - ylidene)hydrazono]-1H-2-indolinones (3a-i/4) were synthesized from the reaction of 3-(4-substituted-3-thiosemicarbazono-1H-2-indolinones (1a-I) with 2-chloroacetoacetic acid ethyl ester (2). All synthesized compounds were characterized by IR, 1H-NMR, EIMS and elementary analysis.

Synthesis and antimicrobial activity of some 5-aryl-2-[N,N-disubstituted thiocarbamoylthio)acylamino]-1,3,4-oxadiazoles.

In this study, a number of novel 5-aryl-2-[(N,N-disubstituted thiocarbamoylthio)acylamino]-1,3,4-oxadiazole derivatives were synthesized by the reaction of potassium salts of N,N-disubstituted dithiocarbamoic acids with 2-[(alpha-chloro-alpha-phenylacetyl/alpha-bromopropionyl)-amino]-5 -aryl-1, 3,4-oxadiazoles. Structures of the compounds were confirmed by the spectral data (IR, 1H NMR, EIMS) and elemental analyses. Most of the compounds were tested against various microorganisms and four of them were found to be weakly active against Staphylococcus aureus and Staphylococcus epidermidis.

In vitro and in vivo studies on microcapsules and tabletted microcapsules of cephradine.

Cephradine was microencapsulated by coacervation. Ethyl cellulose was used as the polymer and a core/wall ratio of 1:1 was selected. The repose angle, apparent and tapped density, particle size distribution of cephradine microcapsules (CM) and of cephradine powder were examined. Then flat-surfaced tablets of CM were prepared using Avicel PH 101 and magnesium stearate. In vitro and in vivo properties of CM and tabletted CM (both equivalent to 150 mg cephradine) were compared with commercial capsules (equivalent to 250 mg cephradine). The dissolution studies were carried out by the rotating basket method and the agar diffusion method was applied for quantitative determinations. Among the investigated kinetic models for the release of cephradine from CM and tabletted CM the best fit was found with the Higuchi model. In vivo studies were made in rabbits. Bioavailabilities of CM and their tabletted form were higher than that of the commercial capsules. In vitro/in vivo correlations between mean residence time (MRT) and mean dissolution time (MDT) for CM and tabletted CM were calculated. A good correlation was found between the in vitro and in vivo results.

Postantibiotic effect of imipenem, alone and in combination with amikacin, on Pseudomonas aeruginosa.

Imipenem and amikacin, alone and in combination, were investigated for their postantibiotic effect (PAE) on Pseudomonas aeruginosa. Four clinical strains of P. aeruginosa in the logarithmic phase of growth were exposed for 1 h to antibiotics, alone and in combination. Recovery periods of test cultures were evaluated after dilution using viable counting. Imipenem produced a PAE ranging from 0.7 to 1.55 h. Similar PAEs were induced by amikacin (ranging from 0.65 to 2 h). In combination, imipenem and amikacin produced as a final PAE (ranging from 1.6 to 2.65 h), a rough mathematical sum of the individual effects. The finding of this study may have important implications for the timing of doses during therapy with antimicrobial combinations.

Comparison of imipenem and five other antipseudomonal agents against gentamicin-susceptible and -resistant Pseudomonas aeruginosa.

The in vitro activities of imipenem, aztreonam, piperacillin, ciprofloxacin and amikacin were tested by the microbroth dilution technique against 86 clinical isolates of Pseudomonas aeruginosa. Imipenem and ciprofloxacin were the most active agents against gentamicin-susceptible P. aeruginosa. Only imipenem inhibited gentamicin-resistant P. aeruginosa at < or = 8 micrograms/ml. The finding that none of the gentamicin-resistant strains were resistant to imipenem and amikacin indicated the superiority of these antibiotics to the other agents in hospital-associated gentamicin-resistant P. aeruginosa infections.