Iron(III) complexes: preparation, characterization, antibacterial activity and DNA-binding

Iron(III) have been combined to well known quinolones (ciprofloxacin) and some Schiff bases with the help of coordination approach. Characterization of these compounds have been done using elemental analysis, magnetic measurements, thermogravimetric analysis, IR, UV-VIS, (1)H NMR and (13)C NMR spectral investigation. Analytical studies suggest that the iron(III)-quinolone complexes assume a six-coordinated dimeric distorted octahedral geometry. All the compounds show a good antibacterial activity against broad range of bacteria like Bacillus cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi and Serratia marcescens, whereas no significant inhibition towards growth of fungal strains like Aspergillus Niger, Aspergillus flavus and Lasiodiplodia theobromae. Analyses of all these compounds show effective sperm herring DNA inhibition.     

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.     

Four Natural Compounds Separated from Folium Isatidis: Crystal Structures and Antibacterial Activity

Four natural compounds were obtained by concentrating, separating and purifying from the Folium isatidis. These natural compounds have been characterized by elemental analysis, IR spectrum, NMR and single‐crystal X‐ray diffraction analysis. The results show that these natural compounds are 4(3H)‐quinazolinone ( I ), 2,4(1H,3H)‐quinazolinedione ( II ), methyl 3,4‐dihydro‐4‐oxoquinazoline‐2‐carboxylate ( III ) and ethyl 3,4‐dihydro‐4‐oxoquinazoline‐2‐carboxylate ( IV ). The antibacterial activity experiment showed that I and II had better activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Salmonella than III , IV and other multiple components, because III and IV have long branches and steric hindrance effect. Compounds I and II have planar structure, which can more easily combine with these bacteria and kill them. The above results have good guiding significance for studying the antibacterial activity for single components or mixtures from natural origin.     

Metal based isatin-derived sulfonamides: Their synthesis,characterization, coordination behavior and biological activity

Some isatin derived sulfonamides and their transition metal [Co(II), Cu(II), Ni(II), Zn(II)] complexes have been synthesized and characterized. The structure of synthesized compounds and their nature of bonding have been inferred on the basis of their physical (magnetic susceptibility and conductivity measurements), analytical (elemental analyses) and spectral (IR, ¹H NMR and ¹³C NMR) properties. An octahedral geometry has been suggested for Co(II), Ni(II) and Zn(II) and square-planar for Cu(II) complexes. In order to assess the antibacterial and antifungal behavior, the ligands and their metal(II) complexes were screened for their in vitro antibacterial activity against four Gram-negative species, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi and two Gram-positive species, Staphylococcus aureus and Bacillus subtilis and, for in vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. In vitro cytotoxic properties of all the compounds were also studied against Artemia salina by brine shrimp bioassay. The results of average antibacterial/antifungal activity showed that zinc(II) complexes were found to be the most active against one or more bacterial/fungal strains as compared to the other metal complexes.     

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.     

Solution structure and function of YndB,an AHSA1 protein from Bacillus subtilis

The solution structure of the Bacillus subtilis protein YndB has been solved using NMR to investigate proposed biological functions. The YndB structure exhibits the helix‐grip fold, which consists of a β‐sheet with two small and one long α‐helix, forming a hydrophobic cavity that preferentially binds lipid‐like molecules. Sequence and structure comparisons with proteins from eukaryotes, prokaryotes, and archaea suggest that YndB is very similar to the eukaryote protein Aha1, which binds to the middle domain of Hsp90 and induces ATPase activity. On the basis of these similarities, YndB has been classified as a member of the activator of Hsp90 ATPase homolog 1‐like protein (AHSA1) family with a function that appears to be related to stress response. An in silico screen of a compound library of ～18,500 lipids was used to identify classes of lipids that preferentially bind YndB. The in silico screen identified, in order of affinity, the chalcone/hydroxychalcone, flavanone, and flavone/flavonol classes of lipids, which was further verified by 2D ¹H‐¹⁵N HSQC NMR titration experiments with trans‐chalcone, flavanone, flavone, and flavonol. All of these compounds are typically found in plants as precursors to various flavonoid antibiotics and signaling molecules. The sum of the data suggests an involvement of YndB with the stress response of B. subtilis to chalcone‐like flavonoids released by plants due to a pathogen infection. The observed binding of chalcone‐like molecules by YndB is likely related to thesymbiotic relationship between B. subtilis and plants. Proteins 2010. © 2010 Wiley‐Liss, Inc.     

Synthesis, characterization and antibacterial activity of new sulfonamide derivatives and their nickel(II), cobalt(II) complexes

Methanesulfonicacid hydrazide (a sulfonamide compound, msh: CH₃SO₂NHNH₂) derivatives: methylsalicylaldehydemethanesulfonylhydrazone (5msalmsh), 5-methyl-2-hydroxyaceto-phenonemethanesulfonylhydrazone (5mafmsh) and their Ni(II), Co(II) complexes have been synthesized for the first time. The structure of these sulfonamide compounds has been investigated by using elemental analyses; FT-IR, ¹H NMR, ¹³C NMR, LC-MS, and UV-Vis spectrometric methods; magnetic susceptibility; conductivity measurements; thermal studies. The crystal structure of 5msalmsh has been investigated by X-ray analysis. The antibacterial activities of synthesized compounds were studied against gram positive bacteria: Staphylococcus aureus, Bacillus subtilis, and Bacillus magaterium; and gram negative bacteria: Salmonella enteritidis, and Escherichia coli by using the microdilution broth method. The biological activity screening showed that ligands have more activity than complexes against the tested bacteria.     

Design,synthesis, antimicrobial activity and anti-HIV activity evaluation of novel hybrid quinazoline–triazine derivatives

Abstract

A series of novel hybrid quinazoline–triazine derivatives was designed and synthesized from cyanuric chloride and anthranilic acid through sequential reactions, which contain different pharmacophores like quinazoline and substituted diaryl triazine (DATA) linked with ethylene diamine. All the newly synthesized compounds were characterized by infrared, ¹H-NMR, ¹³C-NMR, MS and elemental analysis. Further, we evaluated the in vitro anti-HIV activity of the newly synthesized compounds against HIV-1 (III_B) and HIV-2 (ROD) viral strains and as well as in vitro antimicrobial activity against four bacteria (Staphylococcus aureus, Bacillus cereus, Pseudomonas aeruginosa, Klebsiella pneumoniae) and two fungi (Aspergillus clavatus, Candida albicans) using the paper agar streak dilution method. The bioassay results indicate that four compounds namely 7d, 7n, 7r and 7s could be considered as possible potential agents.     

Three-dimensional structures of the central regulatory proteins of the bacterial phosphotransferase system,HPr and enzyme IIAglc

Enzyme IIA and HPr are central regulatory proteins of the bacterial phosphoenolpyruvate:sugar phosphotransferase (PTS) system. Three-dimensional structures of the glucose enzyme IIA domain (IIA^glc) and HPr of Bacillus subtilis and Escherichia coli have been studied by both X-ray crystallography and Nuclear Magnetic Resonance (NMR) Spectroscopy. Phosphorylation of HPr of B. subtilis and IIA^glc of E. coli have also been characterized by NMR spectroscopy. In addition, the binding interfaces of B. subtilis HPr and IIA^glc have been identified from backbone chemical shift changes. This paper reviews these recent advances in the understanding of the three-dimensional structures of HPr and IIA^glc and their interaction with each other. © 1993 Wiley-Liss, Inc.     

Biologically Active Heterocyclic Hybrids Based on Quinazolinone,Benzofuran and Imidazolium Moieties: Synthesis,Characterization, Cytotoxic and Antibacterial Evaluation

Cytotoxic and antimicrobial agents structurally based on quinazolinone, benzofuran and imidazole pharmacophores, have been designed and synthesized. Spectral (IR, ¹H‐NMR) and elemental analysis data established the structures of these novel 3‐[1‐(1‐benzofuran‐2‐yl)‐2‐(4‐oxoquinazolin‐3(4H)‐yl)ethyl]‐1‐methyl‐1H‐imidazol‐3‐ium chloride hybrid derivatives. All the synthesized compounds were evaluated for in vitro cytotoxicity and antimicrobial activities. Cytotoxic evaluation using MTT assay revealed that compounds 12c , 12g and 12i exhibited significant cytotoxicity with IC₅₀ values 1, 1, and 0.57 μm on this cell line, respectively. Biological activity of the synthesized compounds as antibacterial agent were also evaluated against three Gram‐negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi), three Gram‐positive (Staphylococcus aureus, Bacillus subtilis and Listeria monocitogenes) and one yeast‐like fungi (Candida albicans) strains. All compounds 12a  –  12i showed slightly higher activity against Gram‐positive bacteria than the Gram‐negative one. Among the nine new compounds screened, 3‐[1‐(5‐bromo‐1‐benzofuran‐2‐yl)‐2‐(6‐chloro‐4‐oxoquinazolin‐3(4H)‐yl)ethyl]‐1‐methyl‐1H‐imidazol‐3‐ium chloride ( 12e ) has pronounced higher antimicrobial activity against all tested strains. These results demonstrated potential importance of molecular hybridization in the development of new lead molecules with major cytotoxicity and antimicrobial activity.     

Acetyl pyridine-based palladium(II) compounds as an artificial metallonucleases

Palladium(II) complexes of type [Pd(Lⁿ)Cl₂] and [Pd(bdt)(Lⁿ)] have been synthesized using 2-acetyl pyridine derivatives(Lⁿ) and benzene-12-dithiol(bdt). The synthesized complexes have been characterized by various analytical techniques like thermo gravimetric analysis, elemental analysis, conductance measurement, and spectroscopic techniques like elemental analysis, mass spectra, absorption spectra, IR, ¹H NMR, energy-dispersive X-ray spectroscopy. The interaction of the complexes with calf-thymus DNA (CT-DNA) has been explored by absorption titration, viscosity measurement methods. Based on the observations, an intercalative binding mode of DNA has been proposed. In order to provide additional evidence for the intercalation mode of binding between the complex and CT-DNA, fluorescence titration experiment was performed. In addition, molecular modeling study has been carried out with the aim of establishing the complex’s binding mode. Antibacterial activity study of the complexes have been screened against pathogenic bacteria such as Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Serratia marcescens, and Pseudomonas aeruginosa. Gel electrophoresis assay demonstrates that all the complexes can cleave the pUC19 plasmid DNA.     

Production,characterization and antimicrobial activities of bio-pigments by Aquisalibacillus elongatus MB592, Salinicoccus sesuvii MB597, and Halomonas aquamarina MB598 isolated from Khewra Salt Range,Pakistan

Hypersaline ecosystems offer unique habitats to microbial populations capable of withstanding extreme stress conditions and producing novel metabolites of commercial importance. Herein, we have characterized for the first time the production of bioactive pigments from newly isolated halophilic bacterial species. Halophilic bacteria were isolated from Khewra Salt Range of Pakistan. Three distinctly colored isolates were selected for pigment production. Selected colonies were identified as Aquisalibacillus elongatus MB592, Salinicoccus sesuvii MB597, and Halomonas aquamarina MB598 based on morphological, biochemical, and physiological evidences as well as 16S rRNA analysis. The optimum pigment production observed at mesophilic condition, nearly neutral pH, and moderate salinity was validated using response surface methodology. Different analytical techniques (UV spectroscopy, infrared spectroscopy, and HPLC) characterized these purified pigments as derivatives of bacterioruberin carotenoids. Antioxidant activity of pigments revealed up to 85% free-radical scavenging activity at the concentration of 30 µg ml⁻¹. Pigments also showed significant antimicrobial activity against Bacillus subtilis, Bacillus pumilus, Enterococcus faecalis, Bacillus cereus, Klebsiella pneumoniae, Alcaligenes faecalis, Pseudomonas geniculata, Enterococcus faecium, Aspergillus fumigatus, Aspergillus flavus, Fusarium solani, and Mucor spp., suggesting potential biomedical applications.

     

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,spectroscopic, and antibacterial activity of tetraazamacrocyclic complexes of trivalent chromium,manganese, and iron

A new series of macrocyclic complexes of type [M(TML)X]X₂, where M = Cr(III), Mn(III), or Fe(III), TML is tetradentate macrocyclic ligand, and X = Cl^?, NO₃^?, CH₃COO^? for Cr(III), Fe(III) and X = CH₃COO^? for Mn (III), has been synthesized by condensation of benzil and succinyldihydrazide in the presence of metal salt. The complexes have been so formulated due to the 1:2 electrolytic nature of these complexes as shown by conductivity measurements. The complexes have been characterized with the help of various physicochemical techniques such as elemental analysis, molar conductance, electronic and infrared spectral studies, and magnetic susceptibility. On the basis of these studies, a five-coordinate distorted square pyramidal geometry, in which two nitrogens and two carbonyl oxygen atoms are suitably placed for coordination toward the metal ion, has been proposed for all the complexes. The complexes have been tested for their in vitro antibacterial activity. Some of the complexes show remarkable antibacterial activities against some selected bacterial strains. The minimum inhibitory concentrations shown by these complexes have been compared with those shown by some standard antibiotics such as linezolid and cefaclor.     

Novel 2-aminopyridine liganded Pd(II) N-heterocyclic carbene complexes: Synthesis,characterization, crystal structure and bioactivity properties

In this work, the synthesis, crystal structure, characterization, and enzyme inhibition effects of the novel a series of 2-aminopyridine liganded Pd(II) N-heterocyclic carbene (NHC) complexes were examined. These complexes of the Pd-based were synthesized from PEPPSI complexes and 2-aminopyridine. The novel complexes were characterized by using ¹³C NMR, ¹H NMR, elemental analysis, and FTIR spectroscopy techniques. Also, crystal structures of the two compounds were recorded by using single-crystal X-ray diffraction assay. Also, these complexes were tested toward some metabolic enzymes like α-glycosidase, aldose reductase, butyrylcholinesterase, acetylcholinesterase enzymes, and carbonic anhydrase I, and II isoforms. The novel 2-aminopyridine liganded (NHC)PdI₂(2-aminopyridine) complexes (1a-i) showed Ki values of in range of 5.78 ± 0.33–22.51 ± 8.59 nM against hCA I, 13.77 ± 2.21–30.81 ± 4.87 nM against hCA II, 0.44 ± 0.08–1.87 ± 0.11 nM against AChE and 3.25 ± 0.34–12.89 ± 4.77 nM against BChE. Additionally, we studied the inhibition effect of these derivatives on aldose reductase and α-glycosidase enzymes. For these compounds, compound 1d showed maximum inhibition effect against AR with a Ki value of 360.37 ± 55.82 nM. Finally, all compounds were tested for the inhibition of α-glycosidase enzyme, which recorded efficient inhibition profiles with Ki values in the range of 4.44 ± 0.65–12.67 ± 2.50 nM against α-glycosidase.     

Synthesis and biological evaluation of some dibenzofuran-piperazine derivatives

In the present paper, a novel series of dibenzofuran-piperazine derivatives were synthesized via the treatment of N-(2-methoxy-3-dibenzofuranyl)-2-chloroacetamide with substituted piperazine derivatives. The chemical structures of the compounds were elucidated by ¹H NMR, ¹³C NMR, mass spectral data; elemental analysis and HPLC analysis. Each derivative was evaluated for antiplatelet activity and anticholinesterase activity. Compound 2?m with 2-furoyl moiety exhibited high percentage inhibition as much as standard drug aspirin on arachidonic acid (AA)-induced platelet aggregation. None of the compounds presented significant inhibitor effect on collagen-induced platelet aggregation. Furthermore, the anticholinesterase activity of the compounds was determined and they did not show promising inhibitor activity compared with standard drug donepezil.     

Synthesis and characterization of some metal complexes of a proton transfer salt,and their inhibition studies on carbonic anhydrase isozymes and the evaluation of the results by statistical analysis

Abstract

A novel proton transfer compound (HMeOABT)?⁺?(HDPC)^? (1) and its Fe(III), Co(II), Ni(II) and Cu(II) complexes (2–5) have been prepared and characterized by spectroscopic techniques. Complex 4 has distorted octahedral conformation revealed by single crystal X-ray diffraction method. Structures of the other complexes might be proposed as octahedral according to experimental data. All compounds were also evaluated for their in vitro inhibition effects on hCA I and II for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA I and II. Data have been analyzed by using a one-way analysis of variance. The comparison of the inhibition studies of 1–5 to parent compounds indicates that 1–5 have superior inhibitory effects. The inhibition effects of 2–5 are also compared to inhibitory properties of the metal complexes of MeOABT and H2DPC, revealing an improved transfection profile.     

Metal-based ethanolamine-derived compounds: a note on their synthesis,characterization and bioactivity

Abstract

Metal-based ethanolamines, (L¹)–(L⁴) coordinated with Co(II), Cu(II), Ni(II) and Zn(II) metals in 1:2 (metal:ligand) molar ratio to produce new compounds have been reported. These compounds were screened for their bactericidal/fungicidal activity against a number of bacterial (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi, Staphylococcus aureus and Bacillus subtilis) and fungal strains (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata) alongside against a shrimp species known as Artemia salina. The screening results indicated that metal complexes have significantly higher activity than uncomplexed ligands against one or more bacterial/fungal species due to chelation. The ligand (L⁴) displayed good bacterial and fungal activity as compared to other ligands. The antibacterial results revealed that the Zn(II) complex (16) of (L⁴) was found to be the most active complex and Co(II) complex (14) of the same ligand (L⁴), demonstrated the highest antifungal activity.     

Biosynthesis of isotopically labeled gramicidins and tyrocidins by Bacillus brevis

The three-dimensional structure of bilayer-associated gramicidin A is available from a structural data base. This and related peptides are, therefore, ideal model compounds to use during the implementation and development of new NMR techniques for the structural investigations of membrane proteins. As these methods rely on the isotopic labelling of single, selected or all sites, we have, investigated and optimised biochemical protocols using different strains of the Gram-positive bacterium Bacillus brevis. With newly developed schemes for isotopic labelling large amounts of gramicidin and tyrocidin enriched with stable isotopes such as ¹⁵N or ¹⁵N/¹³C have been obtained at low cost. A variety of analytical and spectroscopic techniques, including HPLC, mass spectrometry and NMR spectroscopy are used to characterise the resulting products.     

Synthesis, stereochemistry and in vitro antimicrobial evaluation of novel 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-4-phenyl-2,3-dihydrothiazoles

2-[(2,4-Diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-4-phenyl-2,3-dihydrothiazoles (3a-3k) have been synthesized by the cyclization of 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones with phenacyl bromide and characterized by analytical (melting point and elemental analysis) and spectral (IR, (1)H NMR, (13)C NMR, D(2)O exchange, NOESY and mass) techniques. The novel Hantzsch products (3a-3k) were screened for their in vitro antibacterial and antifungal activities against some selected microorganisms. Structure activity relationship (SAR) for the reported compounds was studied by comparing their MIC values with standard drugs (Streptomycin and Amphotericin B). The results show that 3e against Escherichia coli and Cryptococcus neoformans3i against Bacillus Subtilis, 3b against Aspergillus flavus, and 3k against Rhizopus sp. were found to show significant growth inhibition.