Antimicrobial activity of a series of thiosemicarbazones and their Zn<Superscript>II</Superscript> and Pd<Superscript>II</Superscript> 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 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-R^5′-phenyl)-1H-benzimidazoles and their Fe^III, Cu^II, Ag^I, Zn^II and Hg^II nitrate complexes was tested towardStaphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella flexneri, andProteus mirabilis. Antifungal activity was tested againstCandida albicans. Benzimidazole benzene ring substituents increase the antimicrobial activity, phenol ring substituents decrease it. The ligands show an antibacterial effect against onlyS. aureus whereas Ag^I and Hg^II complexes of the ligands have a higher activity with respect to the other complexes to all the bacteria. On the other hand, Fe^III complexes show a considerable activity againstS. aureus andS. epidermidis.     

Inhibitory and antimicrobial activities of OGTI and HV-BBI peptides, fragments and analogs derived from amphibian skin

A series of linear and cyclic fragments and analogs of two peptides (OGTI and HV-BBI) isolated from skin secretions of frogs were synthesized by the solid-phase method. Their inhibitory activity against several serine proteinases: bovine β-trypsin, bovine α-chymotypsin, human leukocyte elastase and cathepsin G from human neutrophils, was investigated together with evaluation of their antimicrobial activities against Gram-negative bacteria (Escherichia coli) and Gram-positive species isolated from patients (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus sp., Streptococcus sp.). The cytotoxicity of the selected peptides toward an immortal human skin fibroblast cell line was also determined. Three peptides: HV-BBI, its truncated fragment HV-BBI(3-18) and its analog [Phe(8)]HV-BBI can be considered as bifunctional compounds with inhibitory as well as antibacterial properties. OGTI, although it did not display trypsin inhibitory activity as previously reported in the literature, exerted antimicrobial activity toward S. epidermidis. In addition, under our experimental conditions, this peptide did not show cytotoxicity.     

Synthesis and pharmacological activities of some mononuclear Ru(II) complexes

A series of mononuclear Ru(II) complexes of the type [Ru(M)2(U)]2+, where M = 2,2'-bipyridine/1,10-phenanthroline and U = tpl (Ru1), 4-Cl-tpl (Ru2), 4-CH3-tpl (Ru3), 4-CH3O-tpl (Ru4), and 4-NO2-tpl (Ru5), -pai (Ru6), where tpl = thiopicolinanilide and pai = 2-phenyl-azo-imidazole, have been prepared and characterized by IR, UV-Vis, 1H NMR, 13C-NMR, FAB-Mass spectrophotometer, and elemental analysis. The complexes display metal-ligand charge transfer (MLCT) transitions in the visible region. The title complexes were subjected to in vivo anticancer activity tests against a transplantable murine tumor cell line, Ehrlich's ascitic carcinoma (EAC) and in vitro antibacterial activity against Gram positive and Gram negative microorganisms. Ru1-Ru6 were found to increase the life span of the tumor hosts by 19-52%, and decreased tumor volume and viable ascitic cell count. The results of the present study clearly demonstrated the tumor inhibitory activity of the ruthenium chelates against transplantable murine tumor cell line. The treatment with ruthenium complexes could be secondary to tumor regression or due to the action of the compounds itself. The significant antibacterial activity was observed for Ru1-Ru4 against microorganisms like Vibrio cholera 865, Staphylococcus aureus 6571, and Shigella flexneri as compared to that of standard drug chloramphenical. Ru5 showed moderate activity against S. aureus 8530. However, all the complexes fail to show significant antibacterial activity against V. cholera 14033 and Shigella sonnai.     

Synthesis and antibacterial activity of 1-[1,2,4-triazol-3-yl] and 1-[1,3,4-thiadiazol-2-yl]-3-methylthio-6,7-dihydrobenzo[c]thiophen-4(5H)ones

A series of 1-[1,2,4-triazol-3-yl] and 1-[1,3,4-thiadiazol-2-yl]-3-methylthio-6,7-dihydrobenzo[c]thiophen-4(5H)ones were synthesized and tested to demonstrate in vitro antimicrobial activity. Some of these compounds exhibited a good activity against Staphylococcus aureus, S. epidermidis and Bacillus subtilis.     

Antimicrobial activity of hydrophobic xanthones from Cudrania cochinchinensis against Bacillus subtilis and methicillin-resistant Staphylococcus aureus

Ten xanthones with one or two isoprenoid groups and a prenylated benzophenone isolated from roots of Cudrania cochinchinensis (Moraceae) were tested for their antimicrobial activities against Bacillus subtilis and methicillin-resistant Staphylococcus aureus (MRSA). Among these compounds, gerontoxanthone H exhibited considerable antibacterial activity against B. subtilis (MIC = 1.56 microg/ml). Four xanthones, gerontoxanthone I, toxyloxanthone C, cudraxanthone S, and 1,3,7-trihydroxy-2-prenylxanthone, showed weak antibacterial activity against the bacterium (MICs = 3.13-6.25 microg/ml). These compounds also exhibited similar MIC values against methicillin-sensitive S. aureus, MRSAs, and Micrococcus luteus.     

Design, synthesis, and structure-activity relationship studies of conformationally restricted mutilin 14-carbamates

We report herein the design, synthesis, and structure-activity relationship studies of conformationally restricted mutilin 14-carbamates based on the structure of SB-222734. The antibacterial activities of these newly synthesized compounds were also evaluated and compared with linezolid and retapamulin. Results showed that most of the target compounds exhibit good potency in inhibiting the growth of Gram-positive bacteria including Methicillin-susceptible Staphylococcus aureus MSSA (MIC: 0.0625-2μg/mL), Methicillin-resistant S. aureus MRSA (MIC: 0.0625-2μg/mL), Methicillin-susceptible Staphylococcus epidermidis MSSE (MIC: 0.0625-2μg/mL), Methicillin-resistant S. epidermidis MRSE (MIC: 0.0625-2μg/mL), and Streptococcus pneumonia (MIC: 0.0625-4μg/mL). In particular, three remarkable compounds of this series (12l, 12m, and 21l) exhibited comparable in vitro antibacterial profiles to that of retapamulin.     

Antibacterial action of a heat-stable form of L-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom

The major l-amino acid oxidase (LAAO, EC 1.4.3.2) of king cobra (Ophiophagus hannah) venom is known to be an unusual form of snake venom LAAO as it possesses unique structural features and unusual thermal stability. The antibacterial effects of king cobra venom LAAO were tested against several strains of clinical isolates including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli using broth microdilution assay. For comparison, the antibacterial effects of several antibiotics (cefotaxime, kanamycin, tetracycline, vancomycin and penicillin) were also examined using the same conditions. King cobra venom LAAO was very effective in inhibiting the two Gram-positive bacteria (S. aureus and S. epidermidis) tested, with minimum inhibitory concentration (MIC) of 0.78μg/mL (0.006μM) and 1.56μg/mL (0.012μM) against S. aureus and S. epidermidis, respectively. The MICs are comparable to the MICs of the antibiotics tested, on a weight basis. However, the LAAO was only moderately effective against three Gram-negative bacteria tested (P. aeruginosa, K. pneumoniae and E. coli), with MIC ranges from 25 to 50μg/mL (0.2-0.4μM). Catalase at the concentration of 1mg/mL abolished the antibacterial effect of LAAO, indicating that the antibacterial effect of the enzyme involves generation of hydrogen peroxide. Binding studies indicated that king cobra venom LAAO binds strongly to the Gram-positive S. aureus and S. epidermidis, but less strongly to the Gram-negative E. coli and P. aeruginosa, indicating that specific binding to bacteria is important for the potent antibacterial activity of the enzyme.     

Antibacterial prenylflavone derivatives from Psoralea corylifolia, and their structure-activity relationship study

Three new prenylflavonoids, namely corylifols A-C (1-3), together with 13 known ones, were isolated from the seeds of Psoralea corylifolia. Their structures were elucidated by spectral methods including 1D and 2D NMR techniques. All the isolates were tested on antibacterial assays, and nine of them showed significant antibacterial activities against two pathogenic bacteria Staphylococcus aureus and S. epidermidis. The antibacterial structure-activity relationship of these prenylflavonoids (1-16) was also briefly discussed.     

Some bivalent metal complexes of Schiff bases containing N and S donor atoms

Schiff bases have been synthesized by the reaction of p-nitrobenzaldehyde, o-nitrobenzaldehyde and p-toluyaldehyde with 4-amino-5-mercapto-1,2,4-triazole. The ligands react with Co(II), Ni(II) and Zn(II) metals to yield (1:1) and (1:2) [metal:ligand] complexes. Elemental analyses, IR, 1H NMR, electronic spectral data, magnetic susceptibility measurements, molar conductivity measurements and thermal studies have investigated the structure of the ligands and their metal complexes. The electronic spectral data suggests octahedral geometry for Co(II), Ni(II) and Zn(II). The antibacterial activities of the ligands and their metal complexes have been screened in vitro against three Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative (Salmonella typhi and Pseudomonas aeruginosa) organisms. The coordination of the metal ion had a pronounced effect on the microbial activities of the ligands and the metal complexes have higher antimicrobial effect than the free ligands.     

Antimicrobial activity of diterpenoids from hairy roots of Salvia sclarea L.: Salvipisone as a potential anti-biofilm agent active against antibiotic resistant Staphylococci

The antimicrobial activities of crude dichloromethane fractions from acetone extracts of Agrobacterium rhizogenes transformed roots and roots of field-grown plants of Salvia sclarea as well as four pure abietane diterpenoids isolated from the hairy root cultures were determined. The growth of Gram-positive bacteria (Staphylococcus aureus, S. epidermidis, Enterococcus faecalis) but not Gram-negative ones (Escherichia coli, Pseudomonas aeruginosa) or pathogenic fungi (Candida albicans) was inhibited by fractions tested at concentrations of 37.5-75.0 microgml(-1). Abietane diterpenoids: salvipisone, aethiopinone, 1-oxoaethiopinone and ferruginol were shown to be bacteriostatic as well as bacteriocidal for the cultures of S. aureus and S. epidermidis strains, regardless of their antibiotic susceptibility profile. This was demonstrated by using simultaneously the optical density measuring method and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide-reduction assay. The highest activity was shown by salvipisone which demonstrated also a very interesting activity when its effect on 24-h-old staphylococcal biofilm cells viability was examined. It limited the survival of biofilms formed by S. aureus as well as by S. epidermidis, putting this compound to the list of potential anti-biofilm agents, better than most of known antibiotics.     

Organic extracts with antimicrobian activity from Penicillium sp. (Moniliales) isolated from the sponge Ircinia felix (Porifera: Demospongiae)

This research expresses the potential of the bacterial activity present in the organic extracts obtained from Penicillium sp., isolated from the esponge Irciniafelix. This activity was evaluated through agar diffusion test and Minimal Inhibitory Concentration (MIC). The susceptibility trials of organic fractions were carried out against Staphylococcus aureus, S. epidermidis, Bacillus cereus and B. subtilis. The use of the chromatographic techniques (CLV and TLC), permitted to obtain bioactive organic extracts of different polarities, of which only the EtOAc and MeOH fractions inhibited the growth of the bacteria used. Of the EtOAc fractionation, only fraction number 3 EtOAc/Hex presented greatest activity against the Gram-positive bacteria. Number 1 EtOAc/Hex fraction increased its activity against S. aureus (24 mm) and S. epidermidis (25 mm), which can be explained by the loss of possible antagonistic effect during the fractionation process. The CMI trials were carried out for the EtOAc number I subfraction against S. aureus, S. epidermidis, B. cereus and B. subtilis, wich was clinical interest, and shows the potential of this organic extract as antimicrobial agent.     

Isatin-derived antibacterial and antifungal compounds and their transition metal complexes

A series of isatins incorporating thiazole, thiadiazole, benzothiazole and p-toluene sulfonyl hydrazide moieties, along with their cobalt(II), copper(II), nickel(II) and zinc(II) metal complexes have been synthesized and characterized by elemental analyses, molar conductances, magnetic moments, IR, NMR and electronic spectral data. These compounds have been screened for antibacterial activity against Escherichia coli, Bacillus subtillis, Shigella flexneri, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi, and for antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata using the agar-well diffusion method. All the synthesized compounds have shown good affinity as antibacterial and/or antifungal agents which increased in most of the cases on complexation with the metal ions.     

Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl)piperazinyl quinolone derivatives

A series of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl) derivatives of piperazinyl quinolones was synthesized and evaluated for antibacterial activity against Gram-positive and Gram-negative microorganisms. Some of these derivatives exhibit high activity against Gram-positive bacteria; Staphylococcus aureus and Staphylococcus epidermidis, comparable or more potent than their parent N-piperazinyl quinolones norfloxacin and ciprofloxacin as reference drugs. The SAR of this series indicates that both the structure of the benzyl unit and the S or SO(2) linker dramatically impact antibacterial activity.     

Synthesis and antimicrobial activity of N-alkyl and N-aryl piperazine derivatives

A series of substituted piperazine derivatives have been synthesized and tested for antimicrobial activity. The antibacterial activity was tested against Staphylococcus aureus (MTCCB 737), Pseudomonas aeruginosa (MTCCB 741), Streptomyces epidermidis (MTCCB 1824) and Escherichia coli (MTCCB 1652), and antifungal activity against Aspergillus fumigatus, Aspergillus flavus and Aspergillus niger. All synthesized compounds showed significant activity against bacterial strains but were found to be less active against tested fungi. In vitro toxicity tests demonstrated that compounds 4d and 6a showed very less toxicity against human erythrocytes.     

Synthesis, antibacterial activity, and quantitative structure-activity relationships of new (Z)-2-(nitroimidazolylmethylene)-3(2H)-benzofuranone derivatives

A new series of (Z)-2-(1-methyl-5-nitroimidazole-2-ylmethylene)-3(2H)-benzofuranones (11a-p) and (Z)-2-(1-methyl-4-nitroimidazole-5-ylmethylene)-3(2H)-benzofuranones (12a-m) were synthesized and assayed for their antibacterial activity against Gram-positive and Gram-negative bacteria. Most of the 5-nitroimidazole analogues (11a-p) showed a remarkable inhibition of a wide spectrum of Gram-positive bacteria (Staphylococcus aureus, Streptococcus epidermidis, MRSA, and Bacillus subtilis) and Gram-negative Klebsiella pneumoniae, whereas 4-nitroimidazole analogues (12a-m) were not effective against selected bacteria. The quantitative structure-activity relationship investigations were applied to find out the correlation between the experimentally evaluated activities with various parameters of the compounds studied. The QSAR models built in this work had reasonable predictive power and could be explained by the observed trends in activities.     

In-vitro antibacterial, antifungal and cytotoxic properties of metal-based furanyl derived sulfonamides

A new series of antibacterial and antifungal furanyl-derived sulfonamides and their cobalt (II), copper (II), nickel (II) and zinc (II) metal complexes have been synthesized, characterized and screened for their in-vitro antibacterial activity against four Gram-negative (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi) and two Gram-positive (Bacillus subtilis and Staphylococcus aureus) bacterial strains and, for in-vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. The results of these studies revealed that all compounds showed significant to moderate antibacterial activity. However, the zinc (II) complexes were found to be comparatively much more active as compared to the others. For antifungal activity generally, compounds (22) and (24) showed significant activity against Escherichia coli (a), (6) against Shigella flexeneri (b), (16) and (22) against Pseudomonas aeruginosa (c), (14) and (16) against Salmonella typhi (d), (9) against Staphylococcus aureus (e) and, (14) and (16) against Bacillus subtilis (f) fungal strains. The brine shrimp (Artemia salina) bioassay was also carried out to study their in-vitro cytotoxic properties. Only three compounds, (6), (10) and (23) displayed potent cytotoxic activity with LD50 = 1.8535 x 10(-4), 1.8173 x 10(-4) and 1.9291 x 10(-4) respectively.     

Complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin. A study of their antimicrobial activity

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin (HL(1) and HL(2), respectively) were synthesized and characterized, being the crystal structures of HL(1), HL(2) and [Ni(L(1))(2)].2CHCl(3) elucidated by X-ray diffraction techniques. The in vitro antimicrobial activity of all these compounds was tested against several bacteria and fungi. HL(1)and its complexes exhibited a strong inhibition of the growth of Haemophilus influenzae (MIC 0.15-1.50microg/mL) and good antibacterial properties towards Bacillus subtilis (MIC 3-25microg/mL). The minimal inhibitory concentration (MIC) was defined as the lowest concentration of compound inhibiting the growth of each strain. The antibacterial effectiveness was confirmed against a number of Gram positive bacteria, including methicillin-resistant Staphylococcus aureus. Yeasts and moulds showed a low susceptibility, except the dermatophyte mould Epidermophyton floccosum that is inhibited at concentrations ranging from 6 to 50microg/mL. In general, the antimicrobial activity of the thiophene derivatives was greater than that of the isonicotinic analogues.