In-vitro antibacterial, antifungal and cytotoxic activities of some coumarins and their metal complexes

A series of new antibacterial and antifungal coumarin-derived compounds and their transition metal complexes [cobalt (II), copper (II), nickel (II) and zinc (II)] have been synthesized, characterized and screened for their in vitro antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigella dysenteriae, Bacillus cereus, Corynebacterium diphtheriae, Staphylococcus aureus and Streptococcus pyogenes bacterial strains and for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani, Candida glaberata. The results of these studies show the metal complexes to be more antibacterial and antifungal as compared to the uncomplexed coumarins. The brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties.     

In vitro cytotoxic,antibacterial, antifungal and urease inhibitory activities of some N4- substituted isatin-3-thiosemicarbazones

A series of 15 previously reported N⁴-substituted isatin-3-thiosemicarbazones 3a-o has been screened for cytotoxic, antibacterial, antifungal and urease inhibitory activities. Compounds 3b, 3e and 3n proved to be active in cytotoxicity assay; 3e exhibited a high degree of cytotoxic activity (LD₅₀ = 1.10 × 10^{? 5} M). Compound 3h exhibited significant antibacterial activity against B. subtilis, whereas compounds 3a, 3k and 3l displayed significant antifungal activity against one or more fungal strains i.e. T. longifusus, A. flavus and M. canis. In human urease enzyme inhibition assay, compounds 3g, 3k and 3m proved to be the most potent inhibitors, exhibiting relatively pronounced inhibition of the enzyme. These compounds, being non-toxic, could be potential candidates for orally effective therapeutic agents to treat certain clinical conditions induced by bacterial ureases like H. pylori urease. This study presents the first example of inhibition of urease by isatin-thiosemicarbazones and as such provides a solid basis for further research on such compounds to develop more potent inhibitors.     

Synthesis,antibacterial and antifungal activities of some carbazole derivatives

A series of N-substituted carbazole derivatives were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Bacillus proteus, Candida albicans and Aspergillus fumigatus by two fold serial dilution technique. Some of the synthesized compounds displayed comparable or even better antibacterial and antifungal activities than reference drugs fluconazole, chloramphenicol and norfloxacin against tested strains.     

Template synthesis,spectroscopic, antibacterial,and antifungal studies of trivalent transition metal ion macrocyclic complexes

A novel series of complexes of the type [M(C₃₆H₂₂N₆)X]X₂, where M = Cr(III), Mn(III), Fe(III); X = Cl^?, NO₃^?, CH₃COO^?; and (C₃₆H₂₂N₆) corresponds to the tetradentate macrocyclic ligand, have been synthesized by condensation of 1,8-diaminonaphthalene and isatin in the presence of trivalent metal salts in methanolic medium. The complexes have been characterized by elemental analysis, conductance and magnetic measurements, and UV/Vis, IR, and mass spectroscopy. On the basis of these studies, a five coordinate square pyramidal geometry for all of these complexes is proposed. All synthesized macrocyclic complexes have been tested for in vitro antimicrobial activities against some pathogenic bacterial strains, viz. Staphylococcus aureus, Bacillus subtilis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and two fungal strains, viz. Aspergillus niger, Aspergillus flavus. The MICs shown by the complexes against these microbial strains have been compared with MICs shown by standard antibiotic ciprofloxacin and the antifungal drug amphotericin-B.     

Antibacterial,antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones

1‐phenyl‐3‐methyl‐4‐benzoyl‐5‐pyrazolone 4‐ethyl‐thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C₂H₅OH·( 1 ), [Cu(L)₂]·H₂O ( 2 ), [Cu(L)(Br)]·H₂O·CH₃OH ( 3 ), [Cu(L)(NO₃)]·2C₂H₅OH ( 4 ), [VO₂(L)]·2H₂O ( 5 ), [Ni(L)₂]·H₂O ( 6 ), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, ¹H NMR and ¹³C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico‐chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) ( 2 , 4 ), and vanadium(V) ( 5 ) complexes have been determined by single‐crystal X‐ray diffraction. The composition of the coordination polyhedron of the central atom in 2 , 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4 , it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL‐60 cells was tested.     

Thermal solvent-free synthesis of chromonyl chalcones, pyrazolines and their in vitro antibacterial, antifungal activities

A facile and ecofriendly synthesis of new chromonyl chalcones 3a-b from 3-formylchromone 1 and active methyl compounds 2a-b is reported under thermal solvent-free heating condition in good yields. The chromonyl chalcones 3a-b were used as intermediates under green condition for the synthesis of new bioactive pyrazoline derivatives 4a-f. The compounds were tested for antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. The investigation of antimicrobial screening revealed that compounds 3a-b and 4a-f showed antibacterial and antifungal activities.     

In vitro antifungal activity of metal complexes of a quaternized chitosan derivative with copper ions

Antifungal activity of synthetic metal complexes of quaternized N-(propyl) chitosan derivatives with Сu(II) against yeastlike (Saccharomyces cereviseae, Rodothorula rubra, and Candida albicans) and mycelial fungi (Fusarium oxysporum, Alternaria alternata, Cladosporium herbarum) was studied. In vitro application (at 250?500 μg/mL) of the metal complex of quaternized N-(propyl) derivative of low-molecular chitosan with 53% substitution and 1.3% copper ions proved efficient against F. оxysporum, one of ten most common fungal plant pathogens. Water-soluble quaternized N-(propyl) chitosan derivatives with 40?58% degree of substitution were synthesized using glycidyltrimethylammonium chloride under optimally adjusted conditions. Metal complexes of the chitosan derivative with 53% degree of substitution with Сu(II) ions were obtained by dialysis. The quantity of copper ions in the metal complexes was determined by atomic emission spectrometry. The structure of chitosan derivatives was confirmed by spectral analysis (IR, ¹H NMR).     

Thermal solvent-free synthesis of chromonyl chalcones,pyrazolines and their in vitro antibacterial,antifungal activities

A facile and ecofriendly synthesis of new chromonyl chalcones 3a-b from 3-formylchromone 1 and active methyl compounds 2a-b is reported under thermal solvent-free heating condition in good yields. The chromonyl chalcones 3a-b were used as intermediates under green condition for the synthesis of new bioactive pyrazoline derivatives 4a-f. The compounds were tested for antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. The investigation of antimicrobial screening revealed that compounds 3a-b and 4a-f showed antibacterial and antifungal activities.     

Eco-friendly synthesis and in vitro antibacterial activities of some novel chalcones

Chalcone derivatives have been synthesized by reaction of 1-(2,5-dimethyl-furan-3-yl)-ethanone with corresponding active aldehyde in ethanolic NaOH in microwave oven. The structure of these compounds was established by elemental analysis, IR, ¹H NMR, ¹³C NMR, and EI-MS spectral analysis. The anti-bacterial activity of these compounds was first tested in vitro by the disc diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) was determined with the reference of standard drug chloramphenicol. The results showed that pyrazol containing chalcone (compound 8) inhibited both types of bacteria (Gram-positive and Gram-negative) better than chloramphenicol.     

Mononuclear metal complexes with piroxicam: synthesis, structure and biological activity

Piroxicam (=Hpir) is a non-steroidal anti-inflammatory and an anti-arthritic drug. VO(2+), Mn(2+), Fe(3+), MoO(2)(2+) and UO(2)(2+) complexes with deprotonated piroxicam have been prepared and characterized with the use of infrared, UV-Vis, nuclear magnetic resonance and electron paramagnetic resonance spectroscopies. The experimental data suggest that piroxicam acts as a deprotonated bidentate ligand in all complexes and is coordinated to the metal ion through the pyridine nitrogen and the amide oxygen. Molecular mechanics calculations in the gas state have been performed in order to propose a model for the Fe(3+), VO(2+) and MoO(2)(2+) complexes. Potential anticancer cytostatic and cytotoxic effects of piroxicam complexes with VO(2+), Mn(2+) and MoO(2)(2+) on human promyelocytic leukemia HL-60 cells have been investigated. Among all complexes, only VO(pir)(2)(H(2)O) clearly induces apoptosis after 24-h incubation, whereas piroxicam induces apoptosis after 57-h incubation.     

In vitro antifungal and antibacterial activities of extracts of Galium tricornutum subsp. longipedunculatum

The aim of this study was to evaluate the antimicrobial activity of crude ethanolic extracts and fractions of the ariel parts and the fruits of Galium tricornutum subsp. longipedunculatum, traditionally used in northern areas of Pakistan for treating microbial infections of skin. Extracts and their fractions were tested against six bacteria and six fungal strains using the hole diffusion method and macrodilution method. All extracts and fractions possessed significant antimicrobial effect. Four fungal strains, Candida albicans, Trichophyton longifusus, Fusarium.solani and Candida glabrata, showed interesting susceptibility profiles when evaluated using the extracts and fractions with MICs ranging from 0.18 to 200 mg/mL. In case of bacterial strains, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi were significantly susceptible to the extracts and fractions with MICs ranging from 0.12 to 200 mg/mL. Comparative results were carried out using imepenem, miconazole and amphotericin B as standard antibiotics.     

In vitro antifungal and antibacterial activities of extracts of Galium tricornutum subsp. longipedunculatum

The aim of this study was to evaluate the antimicrobial activity of crude ethanolic extracts and fractions of the ariel parts and the fruits of Galium tricornutum subsp. longipedunculatum, traditionally used in northern areas of Pakistan for treating microbial infections of skin. Extracts and their fractions were tested against six bacteria and six fungal strains using the hole diffusion method and macrodilution method. All extracts and fractions possessed significant antimicrobial effect. Four fungal strains, Candida albicans, Trichophyton longifusus, Fusarium.solani and Candida glabrata, showed interesting susceptibility profiles when evaluated using the extracts and fractions with MICs ranging from 0.18 to 200 mg/mL. In case of bacterial strains, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi were significantly susceptible to the extracts and fractions with MICs ranging from 0.12 to 200 mg/mL. Comparative results were carried out using imepenem, miconazole and amphotericin B as standard antibiotics.     

Synthesis,antibacterial and antifungal activities of 3-(1,2,4-triazol-3-yl)-4-thiazolidinones

A new series of 3-(1,2,4-triazol-3-yl)-4-thiazolidinone derivatives has been synthesized by the reaction of Schiff bases of 3-amino-1,2,4-triazoles with mercaptoacetic acid and 2-mercaptopropionic acid. Their antibacterial and antifungal activities were evaluated against S. aureus, S. epidermidis, C. albicans and C. glabrata     

In vitro antibacterial activity and antifungal mode of action of flocculosin, a membrane-active cellobiose lipid

Aims:  To investigate the in vitro antibacterial activity and antifungal mode of action of flocculosin, a cellobiose lipid produced by Pseudozyma flocculosa .
Methods and Results:  When tested against clinical bacterial isolates, the compound was particularly active against Gram-positive bacteria and its effect was not mitigated against isolates known as resistant to other antibiotics. The antifungal activity of flocculosin was found to be rapid and concentration-dependent. At lethal concentrations against Candida albicans , flocculosin caused a rapid leakage of intracellular potassium and inhibited acidification of the medium by plasma membrane ATPases suggesting a physical rather than a biochemical effect. TEM observations of cells exposed 6 h to flocculosin revealed disrupted membranes and disorganized mitochondria.
Conclusions:  Data obtained in this study confirm that flocculosin acts by disrupting the membrane surface of sensitive micro-organisms.
Significance and Impact of the Study:  The elucidation of an antifungal mode of action of flocculosin can be exploited in furthering its antimicrobial potential against fungi and bacteria whose cell membranes are particularly sensitive to the action of the molecule.     

Unexpected formation of 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones: synthesis, antibacterial and antifungal activities

New 3-chloro-1-hydroxy-2,6-diarylpiperidin-4-ones 18-22 were synthesized, characterized by melting point, elemental analysis, MS, FT-IR, one-dimensional NMR ((1)H & (13)C) spectroscopic data and evaluated for their in vitro antibacterial and antifungal activities. All the newly synthesized compounds exerted a wide range of antibacterial activities against the entire tested gram-positive and gram-negative bacterial strains except Escherichia coli. Compounds 21 and 22 exerted strong antifungal activities against Aspergillus flavus, mucor and Microsporum gypsuem. In addition, compound 20 was more potent against Rhizopus.     

Synthesis of organometallic-based biologically active compounds: In vitro antibacterial, antifungal and cytotoxic properties of some sulfonamide incorporated ferrocences

Sulfonamides incorporated ferrocene (SIF) have been synthesized by the condensation reaction of sulfonamides (sulfanilamide, sulfathiazole or sulfamethaxazole) with 1,1'-diacetylferrocene. The synthesized compounds (SIF(1)-SIF(4)) have been characterized by their physical, spectral and analytical properties and have been screened for their in vitro antibacterial properties against pathogenic bacterial strains e.g., Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis Staphylococcus aureus and Salmonella typhi and for antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata using Agar-well diffusion method. Most of the compounds showed good antibacterial activity whereas, all the compounds exhibited significant antifungal activity. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina.     

Synthesis of organometallic-based biologically active compounds: In vitro antibacterial,antifungal and cytotoxic properties of some sulfonamide incorporated ferrocences

Sulfonamides incorporated ferrocene (SIF) have been synthesized by the condensation reaction of sulfonamides (sulfanilamide, sulfathiazole or sulfamethaxazole) with 1,1′-diacetylferrocene. The synthesized compounds (SIF¹–SIF⁴) have been characterized by their physical, spectral and analytical properties and have been screened for their in vitro antibacterial properties against pathogenic bacterial strains e.g., Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis Staphylococcus aureus and Salmonella typhi and for antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata using Agar-well diffusion method. Most of the compounds showed good antibacterial activity whereas, all the compounds exhibited significant antifungal activity. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina.     

The synthesis of xanthones, xanthenediones, and spirobenzofurans: their antibacterial and antifungal activity

Exposure of the phenol, (5-bromo-2-hydroxyphenyl)(2,4,5-trimethoxyphenyl)methanone 18 to ceric ammonium nitrate (CAN) resulted in the formation of 7-bromo-3,4a-dimethoxy-2H-xanthene-2,9(4aH)-dione 19 and 5-bromo-2',5'-dimethoxy-3H-spiro[benzofuran-2,1'-cyclohexa[2,5]diene]-3,4'-dione 20. The brominated spirobenzofuran 20 was then subjected to Suzuki-Miyaura reactions to give six derivatives 22a-f. These compounds, related diones and xanthones displayed mostly noteworthy antimicrobial activity, particularly towards the yeasts Cryptococcus neoformans and Candida albicans. Diones 15 and 30 displayed significant activity (7.8 μg/mL) against C. albicans and C. neoformans, respectively. Furthermore, dione 10 displayed the most significant activity (3.6 μg/mL) against both yeasts.