Synthesis and antibacterial activity of novel phosphonium salts on the basis of pyridoxine

A series of 13 phosphonium salts on the basis of pyridoxine derivatives were synthesized and their antibacterial activity against clinically relevant strains was tested in vitro. All compounds were almost inactive against gram-negative bacteria and exhibited structure-dependent activity against gram-positive bacteria. A crucial role of ketal protection group in phosphonium salts for their antibacterial properties was demonstrated. Among synthesized compounds 5,6-bis[triphenylphosphonio(methyl)]-2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine dichloride (compound 20) was found to be the most effective towards Staphylococcus aureus and Staphylococcus epidermidis strains (MIC 5 μg/ml). The mechanism of antibacterial activity of this compound probably involves cell penetration and interaction with genomic and plasmid DNA.     

Synthesis,antiprotozoal and antibacterial activity of nitro- and halogeno-substituted benzimidazole derivatives

Two series of benzimidazole derivatives were sythesised. The first one was based on 5,6-dinitrobenzimidazole, the second one comprises 2-thioalkyl- and thioaryl-substituted modified benzimidazoles. Antibacterial and antiprotozoal activity of the newly obtained compounds was studied. Some thioalkyl derivatives showed remarkable activity against nosocomial strains of Stenotrophomonas malthophilia, and an activity comparable to that of metronidazole against gram-positive and gram-negative bacteria. Of the tested compounds, 5,6-dichloro-2-(4-nitrobenzylthio)-benzimidazole showed the most distinct antiprotozoal activity.     

Study of ectoparasitism of ultramicrobacteria of the genus Kaistia, strains NF1 and NF3 by electron and fluorescence microscopy

Transmission electron and fluorescence microscopy was used to study the character of the interaction of free-living ultramicrobacterial (UMB) strains NF1 and NF3, affiliated with the genus Kaistia, and seven species of gram-positive and gram-negative heterotrophic bacteria. Strains NF1 and NF3 were found to exhibit parasitic activity against gram-positive Bacillus subtilis and gram-negative Acidovorax delafildii. UMB cells are tightly attached to the envelopes of the victim cells and induce their lysis, thus demonstrating the features of typical ectoparasitism. The selectivity of parasitism of the studied UMB to the victim bacteria has been shown: only two soil microorganisms of the seven test objects, B. subtilis ATCC 6633 and an aerobic gram-negative bacterium A. delafildii 39, were found to be sensitive to UMB attack. Other bacteria (Micrococcus luteus VKM Ac-2230, Staphylococcus aureus 209-P, Pseudomonas putida BS394, Escherichia coli C 600, and Pantoea agglomerans ATCC 27155) were not attacked by UMB. It was established for the first time that free-living UMB may be facultative parasites not only of phototrophic bacteria, as we have previously demonstrated, but of heterotrophic bacteria as well. The UMB under study seem to play an important role in the regulation of the quantity of microorganisms and in the functioning of microbial communities in some natural ecotopes.     

Investigation and identification of the antimicrobial component of the drug "Tomatol"]

Antimicrobial activity of Tomatol against laboratory strains of Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 6538-P and Candida albicans ATCC 885-653 as well as against clinical isolates of Enterobacter spp., Streptococcus spp., Staphylococcus spp., Klebsiella spp. and Escherichia spp. was tested. Tomatol was shown to have a broad antimicrobial spectrum including gram-positive and gram-negative organisms and Candida. The TLC investigation demonstrated that the Tomatol antimicrobial component was that of a complex of organic acids such as succinic, citric, tartaric and others.     

Antimicrobial compounds from Eremophila serrulata

We report a search for antimicrobial compounds in the Australian plant Eremophila serrulata. Bioassay directed fractionation of a diethyl ether extract prepared from the leaves of E. serrulata led to the isolation of two compounds, an omicron-naphthoquinone, 9-methyl-3-(4-methyl-3-pentenyl)-2,3-dihydronaphtho[1,8-bc]pyran-7,8-dione (2), and a serrulatane diterpenoid, 20-acetoxy-8-hydroxyserrulat-14-en-19-oic acid (3). Two other known serrulatane-type diterpenoids, 8,20-dihydroxyserrulat-14-en-19-oic acid (4) and 8,20-diacetoxyserrulat-14-en-19-oic acid (5) were also isolated. None of these compounds had previously been tested for antimicrobial activity. Compounds 2-5 showed antimicrobial activity against Staphylococcus aureus (ATCC 29213) with minimum inhibitory concentrations (MICs) ranging from 15.6 to 250mug/mL. Compound 2 was the most active with an MIC of 15.6mug/mL and a minimum bactericidal concentration (MBC) of 125mug/mL. This compound also showed antimicrobial activity against other Gram-positive bacteria including Streptococcus pyogenes, and Streptococcus pneumoniae. No activity was observed for this compound against all Gram-negative bacteria tested.     

Identification of antimicrobial compounds active against intracellular Staphylococcus aureus

Small-colony variants (SCVs) of Staphylococcus aureus exhibit characteristics of bacteria that can penetrate mammalian cells and remain intracellular and innocuous for indefinite periods. These properties make SCVs a convenient tool that can be used to identify new antibacterial agents having activity against intracellular, quiescent bacteria. Agents active against SCVs could be useful in the treatment of chronic staphylococcal infections such as bovine mastitis. An hemB deletion mutant of S. aureus Newbould, a bovine mastitis isolate, having a stable, genetically defined SCV phenotype, was used in a screening program to identify compounds active against intracellular, gram-positive bacteria. Out of more than 260,000 compounds screened, nine compounds having the desired properties were identified. The range of MICs against gram-positive bacteria was < or = 0.12-32 microg ml-1. One of the compounds (no. 8) showed excellent activity against gram-positive (MICs < or = 0.12 microg ml-1) and gram-negative (MICs < or = 0.12-4 microg ml-1) bacteria. Each of the nine compounds demonstrated efficacy in a neutropenic mouse thigh infection model. Two compounds, including compound no. 8, reduced numbers of bacteria in a mouse mastitis model of infection. Application of a stepwise screening process has identified lead compounds that may be useful for treating persistent, intracellular infections.     

Comparative Study of Antimicrobial Activity of AgBr and Ag Nanoparticles (NPs)

The diverse mechanism of antimicrobial activity of Ag and AgBr nanoparticles against gram-positive and gram-negative bacteria and also against several strains of candida was explored in this study. The AgBr nanoparticles (NPs) were prepared by simple precipitation of silver nitrate by potassium bromide in the presence of stabilizing polymers. The used polymers (PEG, PVP, PVA, and HEC) influence significantly the size of the prepared AgBr NPs dependently on the mode of interaction of polymer with Ag⁺ ions. Small NPs (diameter of about 60–70 nm) were formed in the presence of the polymer with low interaction as are PEG and HEC, the polymers which interact with Ag⁺ strongly produce nearly two times bigger NPs (120–130 nm). The prepared AgBr NPs were transformed to Ag NPs by the reduction using NaBH₄. The sizes of the produced Ag NPs followed the same trends – the smallest NPs were produced in the presence of PEG and HEC polymers. Prepared AgBr and Ag NPs dispersions were tested for their biological activity. The obtained results of antimicrobial activity of AgBr and Ag NPs are discussed in terms of possible mechanism of the action of these NPs against tested microbial strains. The AgBr NPs are more effective against gram-negative bacteria and tested yeast strains while Ag NPs show the best antibacterial action against gram-positive bacteria strains.     

Antimicrobial activity and chemical composition of the essential oil of Nepeta crispa Willd. from Iran

The composition and antimicrobial activity of the essential oil of Nepeta crispa Willd., an endemic species from Iran, was studied. The oil was obtained from the aerial parts of the plant and analyzed by GC and GC/MS. Twenty-three compounds, accounting for 99.8% of the total oil, were identified. The main constituents were 1,8-cineol (47.9%) and 4aalpha,7alpha,7abetanepetalactone (20.3%). The antimicrobial activity of essential oil of N. crispa was tested against seven gram-negative or gram-positive bacteria and four fungi. The results of the bioassays showed the interesting antimicrobial activity, in which the gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus, were the most sensitive to the oil. Also, the oil exhibited a remarkable antifungal activity against all the tested fungi.     

2-Phenyl-5,6-dihydro-2H-thieno[3,2-c]pyrazol-3-ol derivatives as new inhibitors of bacterial cell wall biosynthesis

Twenty-five 2-phenyl-5,6-dihydro-2H-thieno[3,2-c]pyrazol-3-ol derivatives were synthesized for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good inhibitory activity against Staphylococcus aureus MurB, MurC and MurD enzymes in vitro and antimicrobial activity against gram-positive bacteria including MRSA, VRE and PRSP. However, when they were tested in the presence of 4% bovine serum albumin, the MIC values increased to greater than 128 microg/mL against PRSP. None of the compounds demonstrated activity against gram-negative bacteria at MIC <32 microg/mL.     

Antibacterial activity of extracts and neolignans from Piper regnellii (Miq.) C. DC. var. pallescens (C. DC.) Yunck

The evaluation of the activity of the aqueous and ethyl acetate extracts of the leaves of Piper regnellii was tested against gram-positive and gram-negative bacteria. The aqueous extract displayed a weak activity against Staphylococcus aureus and Bacillus subtilis with minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of 1000 micrograms/ml. The ethyl acetate extract presented a good activity against S. aureus and B. subtilis with MIC and MBC at 15.62 micrograms/ml. In contrast to the relative low MICs for gram-positive bacteria, gram-negative bacteria were not inhibited by the extracts at concentrations < or = 1000 mg/ml. The ethyl acetate extract was fractionated on silica gel into nine fractions. The hexane and chloroform fractions were active against S. aureus (MIC at 3.9 micrograms/ml) and B. subtilis (MIC at 3.9 and 7.8 micrograms/ml, respectively). Using bioactivity-directed fractionation, the hexane fraction was rechromatographed to yield the antimicrobial compounds 1, 2, 5, and 6 identified as eupomatenoid-6, eupomatenoid-5, eupomatenoid-3, and conocarpan, respectively. The pure compounds 1 and 2 showed a good activity against S. aureus with MIC of 1.56 micrograms/ml and 3.12 micrograms/ml, respectively. Both compounds presented MIC of 3.12 micrograms/ml against B. subtilis. The pure compound 6 named as conocarpan was quite active against S. aureus and B. subtilis with MIC of 6.25 micrograms/ml. The antibacterial properties of P. regnellii justify its use in traditional medicine for the treatment of wounds, contaminated through bacteria infections.     

Substituted 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones as novel anti-MRSA agents: synthesis, SAR, and in-vitro assessment

In search for a new antibacterial agent with improved antimicrobial spectrum and potency, we designed and synthesized a series of novel 3-((Z)-2-(4-nitrophenyl)-2-(1H-tetrazol-5-yl) vinyl)-4H-chromen-4-ones 7a-h by convergent synthesis approach. All the synthesized compounds were assayed for their in-vitro antibacterial activities against gram-negative and gram-positive bacteria. The preliminary structure-activity relationship, to elucidate the essential structure requirements for the antimicrobial activity that results into anti-MRSA (methicillin-resistant S. aureus) potential, has been described. Amongst the synthesized compounds 7d, 7e, 7f and 7h were found to possess activity against methicillin-resistant S. aureus in addition to the activity against other bacterial strains such as E. faecalis, S. pneumoniae, and E. coli.     

Antibacterial activity of polyphenolic compounds isolated from plants of Geraniaceae and Rosaceae families

Polyphenolic compounds present in extracts of plants belonging to the families Geraniaceae (blood-red cranesbill, wood cranesbill, meadow cranesbill, and alfilaria) and Rosaceae (red raspberry, European dewberry, and tormentil) have been tested for their activity against gram-positive and gram-negative bacteria of the genera Azotobacter, Bacillus, and Pseudomonas. The bacteriostatic activity exhibited some species-related features and depended on the polarity of the extracting agent. The bacteriostatic activity of plant-derived phenolic compounds correlated with their antioxidant potential. The plants of the families Geraniaceae and Rosaceae offer promise as a source of raw material for isolation of polyphenolic compounds exhibiting bactericidal activity, including against opportunistic pathogens (B. cereus, E. coli, P. aeruginosa, and S. aureus strains).     

Antimicrobial activities of some synthesized 1-(3-(2-methylphenyl)-4-Oxo-3<Emphasis Type="Italic">H</Emphasis>-quinazolin-2-yl-4-(substituted)thiosemicarbazide derivatives

The substituted thiosemicarbazide moiety was placed at the C-2 position and 2-methylphenyl group at N-3 position of quinazoline ring and obtained compounds were tested for their antitubercular activities and antibacterial activities against selected gram-positive and gram-negative bacteria. The target compounds 1-(3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl)-4-(substituted) thiosemicarbazides were obtained by the reaction of 2-hydrazino-3-(2-methylphenyl) quinazolin-4(3H)-one with different dithiocarbamic acid methyl ester derivatives. All synthesized compounds were also screened for their antimicrobial activity against selective gram-positive and gram-negative bacteria by agar dilution method. Among the series, 1-[3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl]-4-[4-chlorophenyl]-thiosemicarbazide exhibited the most potent activity against S. typhi, E. coli, and B. subtilis, while 1-[3-(2-methylphenyl)-4-oxo-3H-quinazolin-2-yl]-4-[4-nitrophenyl]-thiosemicarbazide was the most potent against E. coli, B. subtilis, P. aeruginosa, S. typhi, and S. flexneri. These two compounds exhibited the antitubercular activity at the minimum concentration (3 μg/mL) that offered potential for further optimization and development of new antitubercular agents. The obtained results demonstrated promising antimicrobial and antitubercular activities of the synthesized quinazoline compounds which could be used as new scaffolds for improving their antimicrobial activity.     

Trypanocidal and antimicrobial activities of Moquinia kingii.

A chloroform crude extract (aerial part) and two compounds, apigenin (1) and cynaropicrin (2), isolated from Moquinia kingii were evaluated against Trypanosoma cruzi trypomastigotes in vitro. Antimicrobial activity was also screened using twenty-two strains including gram-positive and gram-negative bacteria and the yeasts Candida albicans and C. tropicalis. The chloroform crude extract, fractions and isolated compounds from M. kingii were active for both activities. The IC50 values for trypanocidal activity obtained for cynaropicrin and apigenin were 93.5 microg/ml and 181 microg/ml, respectively, while the minimum inhibitory concentrations (MICs) varied from 100 microg/ml to 2500 microg/ml, against the strains of bacteria and yeasts evaluated.     

Antibacterial activity of a sulfated galactan extracted from the marine alga <Emphasis Type="Italic">Chaetomorpha aerea</Emphasis> against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

The in vitro antimicrobial activity of the marine green algae Chaetomorpha aerea was investigated against gram-positive bacteria, gram-negative bacteria, and a fungus. The water-soluble extract of algae was composed of a sulfated (6.3%) galactan with a molecular weight of 1.160 × 10⁶ Da and a global composition close to commercial polysaccharides, such as dextran sulfate or fucoidan. The polysaccharide was composed of 18% arabinose, 24% glucose, and 58% galactose. The re-suspended extracts (methanol, water) exhibited selective antibacterial activities against 3 gram-positive bacteria including Staphylococcus aureus (ATCC 25923). Minimum inhibitory concentration and minimum bactericidal concentration tests showed that the sulfated galactan could be a bactericidal agent for this strain (40 mg/mL). The results of this study confirmed the potential use of the green algae Chaetomorpha aerea as a source of antibacterial compounds.     

Bromophenols as Candida albicans isocitrate lyase inhibitors

A new series of bromophenols was synthesized by reactions of corresponding phenol analogs with bromine. The synthesized compounds were tested for inhibitory activity against isocitrate lyase (ICL) of Candida albicans and antimicrobial activity against gram-positive and, gram-negative bacteria and fungi. Among the synthesized bromophenols, bis(3-bromo-4,5-dihydroxyphenyl)methanone (11) and (3-bromo-4,5-dihydroxyphenyl)(2,3-dibromo-4,5-dihydroxyphenyl)methanone (12) displayed potent inhibitory activities against ICL, showing a stronger inhibitory effects than were found with natural bromophenol 1. The preliminary structure-activity relationships were investigated in order to determine the essential structural requirements for the inhibitory activities of these compounds against ICL of C. albicans.     

Antimicrobial activity of polycationic peptides

The in vitro activity of six polycationic peptides, buforin II, cecropin P1, indolicidin, magainin II, nisin, and ranalexin, were evaluated against several clinical isolates of gram-positive and gram-negative aerobic bacteria, yeasts, Pneumocystis carinii and Cryptosporidium parvum, by using microbroth dilution methods. The peptides exhibited different antibacterial activities and rapid time-dependent killing. The gram-negative organisms were more susceptible to buforin II and cecropin P1, whereas buforin II and ranalexin were the most active compounds against the gram-positive strains. Similarly, ranalexin showed the highest activity against Candida spp., whereas magainin II exerted the highest anticryptococcal activity. Finally, the peptides showed high anti-Pneumocystis activity, whereas no compound had strong inhibitory effect on C. parvum.     

Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives

As a part of our research to develop novel antitubercular and antimicrobial agents, a series of 3-(4-chlorophenyl)-4-substituted pyrazoles have been synthesised. These compounds were tested for antitubercular activity in vitro against Mycobacterium tuberculosis H37Rv strain using the BACTEC 460 radiometric system, antifungal activity against a pathogenic strain of fungi and antibacterial activity against gram-positive and gram-negative organisms. Among them tested, many compounds showed good to excellent antimicrobial and antitubercular activity. The results suggest that hydrazones, 2-azetidinones and 4-thiazolidinones bearing a core pyrazole scaffold would be potent antimicrobial and antitubercular agents.     

Synthesis and antimicrobial properties of imidazolium and pyrrolidinonium salts

For the purpose of developing new disinfectants and antiseptics, we searched for compounds having high bactericidal activity against gram-positive bacteria, gram-negative bacteria, and fungi. Three different series of quaternary imidazolium and pyrrolidinonium salts were synthesized: series A (1-alkyl-3-methylimidazolium chlorides and bromides); series B (1-alkyl-2-methyl-3-hydroxyethylimidazolium chlorides); and series C (N-alkyl-N-hydroxyethylpyrrolidinonium). Series B and C were newly designed. These three series were tested to evaluate their antibacterial and antifungal properties for the first time. Seven microbial strains were used in the study: Escherichia coli KCTC1924, Salmonella typhimurium KCTC1926, Staphylococcus aureus 209 KCTC1916, Staphylococcus aureus R209 KCTC1928, Bacillus subtilis KCTC1914, Candida albicans KCTC1940, and Chlorella regularis. The antimicrobial efficiency was measured by bacterial and fungal growth inhibition expressed as minimal inhibitory concentration (MIC) values. Series A and B imidazolium salts had very good antimicrobial activity against the examined Gram-negative bacteria, Gram-positive bacteria, and fungi. Also the pyrrolidinonium salt was found to have low MIC for some of tested microorganisms. The antibacterial and antifungal active properties of the salts depend upon the structure of functional groups and the alkyl chain length in the imidazolium and pyrrolidinonium ring. Among the synthesized quaternary imidazolium and pyrrolidinonium salts, the imidazolium salts containing a long alkyl chain and the introduction of a hydroxyethyl chain and methyl group into the imidazolium ring structure leads to broad spectrum active antimicrobial agents which not only have bacteriostatic properties but could be powerful bactericides.