Binding of transition metal ions [cobalt, copper, nickel and zinc] with furanyl-, thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-derived cephalexins as potent antibacterial agents

A method is described for the preparation of novel cephalexin-derived furanyl-, thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-containing compounds showing potent antibacterial activity. The binding of these newly synthesized antibacterial agents with metal ions such as cobalt(II), copper(II), nickel(II) and zinc(II) has been studied and their inhibitory properties against various bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae are also reported. These results suggest that metal ions to possess an important role in the designing of metal-based antibacterials and that such complexes are more effective against infectious diseases compared to the uncomplexed drugs.     

Binding of Transition Metal Ions [Cobalt,Copper, Nickel and Zinc] with Furanyl-, Thiophenyl-, Pyrrolyl-, Salicylyl-and Pyridyl-Derived Cephalexins as Potent Antibacterial Agents

A method is described for the preparation of novel cephalexin-derived furanyl-, thiophenyl-, pyrrolyl-, salicylyl- and pyridyl-containing compounds showing potent antibacterial activity. The binding of these newly synthesized antibacterial agents with metal ions such as cobalt(II), copper(II), nickel(II) and zinc(II) has been studied and their inhibitory properties against various bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae are also reported. These results suggest that metal ions to possess an important role in the designing of metal-based antibacterials and that such complexes are more effective against infectious diseases compared to the uncomplexed drugs.     

Organometallic-based antibacterial and antifungal compounds: transition metal complexes of 1,1'-diacetylferrocene-derived thiocarbohydrazone, carbohydrazone, thiosemicarbazone and semicarbazone

Organometallic-based, 1,1'-diacetylferrocene-derived antibacterial and antifungal thiocarbohydrazone, carbohydrazone, thiosemicarbazone and semicarbazone have been prepared by condensing equimolar amount of 1,1'-diacetylferrocene with thiocarbohydrazide, carbohydrazide thiosemicarbazide and semicarbazide, respectively. These were used as ligands for the preparation of their cobalt (II), copper (II), nickel (II) and zinc (II) metal complexes. All the synthesized ligands and their complexes were characterized by IR, NMR, elemental analyses, molar conductances, magnetic moments and electronic spectral data. These synthesized compounds were screened for their antibacterial activity against Escherichia coli, Bacillus subtillis, 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 compounds showed good antibacterial and antifungal activity which increased on coordination with the metal ions thus, introducing a novel class of organometallic-based antibacterial and antifungal agents.     

Antibacterial Schiff bases of oxalyl-hydrazine/diamide incorporating pyrrolyl and salicylyl moieties and of their zinc(II) complexes

Schiff bases derived from oxaldiamide/oxalylhydrazine and pyrrol-2-carbaldehyde, or salicylaldehyde respectively, as well as their Zn(II) complexes have been prepared and tested as antibacterial agents. These Schiff bases function as tetradentate ligands, forming octahedral Zn(II) complexes. The ketonic form for the diamide derived Schiff base and the enolic form of the hydrazide derived Schiff base were the preferred tautomers for coordination of the metal ions. The title compounds and their Zn(II) derivatives were evaluated for antibacterial activity against several bacterial strains which easily develop resistance to classical antibiotics, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Some of them showed promising biological activity in inhibiting the growth of such organisms.     

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.     

Antibacterial Schiff Bases of Oxalyl-hydrazine/diamide Incorporating Pyrrolyl and Salicylyl Moieties and of Their Zinc(II) Complexes

Schiff bases derived from oxaldiamide/oxalylhydrazine and pyrrol-2-carbaldehyde, or salicylaldehyde respectively, as well as their Zn(II) complexes have been prepared and tested as antibacterial agents. These Schiff bases function as tetradentate ligands, forming octahedral Zn(II) complexes. The ketonic form for the diamide derived Schiff base and the enolic form of the hydrazide derived Schiff base were the preferred tautomers for coordination of the metal ions. The title compounds and their Zn(II) derivatives were evaluated for antibacterial activity against several bacterial strains which easily develop resistance to classical antibiotics, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Some of them showed promising biological activity in inhibiting the growth of such organisms.     

Antibacterial cobalt(II), nickel(II) and zinc(II) complexes of nicotinic acid-derived Schiff-bases

Nicotinic acid derived Schiff bases and their transition metal [cobalt(II), nickel(II) and zinc(II)] complexes have been prepared and characterized by physical, spectral and analytical data. The Schiff bases act as deprotonated tridentate ligands for the complexation of the above mentioned metal ions. These complexes, possessing the general formula [M(L)2] [where M = Co(II), Ni(II) and Zn(II) and L = HL1-HL4] showed an octahedral geometry of the metal ions. For determining the effect of metal ions upon chelation, the Schiff bases and their complexes have been screened for antibacterial activity against several pathogenic strains of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The new metal derivatives reported here were more bactericidal against one or more bacterial species as compared to the uncomplexed Schiff bases.     

Organometallic-based antibacterial and antifungal compounds: transition metal complexes of 1,1′-diacetylferrocene-derived thiocarbohydrazone,carbohydrazone, thiosemicarbazone and semicarbazone

Organometallic-based, 1,1′-diacetylferrocene-derived antibacterial and antifungal thiocarbohydrazone, carbohydrazone, thiosemicarbazone and semicarbazone have been prepared by condensing equimolar amount of 1,1′-diacetylferrocene with thiocarbohydrazide, carbohydrazide thiosemicarbazide and semicarbazide, respectively. These were used as ligands for the preparation of their cobalt (II), copper (II), nickel (II) and zinc (II) metal complexes. All the synthesized ligands and their complexes were characterized by IR, NMR, elemental analyses, molar conductances, magnetic moments and electronic spectral data. These synthesized compounds were screened for their antibacterial activity against Escherichia coli, Bacillus subtillis, 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 compounds showed good antibacterial and antifungal activity which increased on coordination with the metal ions thus, introducing a novel class of organometallic-based antibacterial and antifungal agents.     

Synthesis, characterization and biological studies of sulfonamide Schiff's bases and some of their metal derivatives

A new series of Schiff base ligands derived from sulfonamide and their metal(II) complexes [cobalt(II), copper(II), nickel(II) and zinc(II)] have been synthesized and characterized. The nature of bonding and structure of all the synthesized compounds has been explored by physical, analytical and spectral data of the ligands and their metal(II) complexes. The authors suggest that all the prepared complexes possess an octahedral geometry. The ligands and metal(II) complexes have been screened for their in vitro antibacterial activity against bacterial strains, Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa, Salmonella typhi and for antifungal activity against fungal strains, Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata. These assays enabled the identification of the metal complexes as an effective antimicrobial agent with low cytotoxicity.     

Antibacterial and antifugal mono- and di-substituted symmetrical and unsymmetrical triazine-derived Schiff-bases and their transition metal complexes

A new series of antibacterial and antifungal triazine-derived mono- and di-substituted (symmetrical and unsymmetrical) Schiff-bases and their cobalt(II), copper(II), nickel(II) and zinc(II) metal complexes have been synthesized and characterized by their elemental analyses, molar conductances, magnetic moments and IR and electronic spectral measurements. IR spectra indicated the ligands to act as tridentate towards divalent metal ions via a trazine-N, the azomethine-N and, indole-NH and deprotonated-O of salicylaldehyde. The magnetic moments and electronic spectral data suggest octahedral geometry for the Co(II), Ni(II) and Zn(II)complexes and square-pyramid for Cu(II) complexes. NMR spectral data of the ligands and their diamagnetic zinc(II) complexes well-define their proposed structures/geometries. Elemental analyses data of the ligands and metal complexes agree with their proposed structures/geometries. The synthesized ligands, along with their metal complexes were screened for their 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. The results of these studies show the metal complexes to be more antibacterial/ antifungal against two or more species as compared to the uncomplexed Schiff-base ligands.     

Design,synthesis, and biological properties of triazole derived compounds and their transition metal complexes

Triazole derived Schiff bases and their metal complexes (cobalt(II), copper(II), nickel(II), and zinc(II)) have been prepared and characterized using IR, ¹H and ¹³C NMR, mass spectrometry, magnetic susceptibility and conductivity measurements, and CHN analysis data. The structure of L², N-[(5-methylthiophen-2-yl)methylidene]-1H-1,2,4-triazol-3-amine, has also been determined by the X-ray diffraction method. All the metal(II) complexes showed octahedral geometry except the copper(II) complexes, which showed distorted octahedral geometry. The triazole ligands and their metal complexes have been screened for their in vitro antibacterial, antifungal, and cytotoxic activity. All the synthesized compounds showed moderate to significant antibacterial activity against one or more bacterial strains. It is revealed that all the synthesized complexes showed better activity than the ligands, due to coordination.     

Metal-based biologically active azoles and β-lactams derived from sulfa drugs

Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their β-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, ¹H NMR, ¹³C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1–2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the β-lactam derivatives (3–4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5–8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands.     

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.     

Ligational behavior of a novel biologically active donor toward Cu(II) and Ni(II) ions and potentiation of its antibacterial activity by chelation with metal ions

The chelating behavior of a new multidentate ligand with tuberculostatic activity toward Cu(II) and Ni(II) ions has been studied. This ligand 3-(2-carboxyhydrazine)phenylimino-2-oximobutane(H2C POB) is found to chelate the above metal ions in both its keto and enol forms. The probable structures of all the complexes and the location of the bonding sites have been established through magnetic and spectroscopic (infrared, electronic) studies. The Cu(II) complex of the enol form exhibits subnormal magnetic moment at room temperature, indicating the probable existence of some sort of super exchange phenomenon in the system. The ligand itself and a few of its Cu(II) complexes have been found to exert powerful in vitro antibacterial activity toward some tuberculosis mycobacteria, such as Mycobacterium flae, Mycobacterium smegmatis, and Mycobacterium H37Rv.     

Antimicrobial, spectral, magnetic and thermal studies of Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes of the Schiff base derived from oxalylhydrazide

The Schiff base ligand, oxalic bis[(2-hydroxybenzylidene)hydrazide], H(2)L, and its Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III) complexes were prepared and tested as antibacterial agents. The Schiff base acts as a dibasic tetra- or hexadentate ligand with metal cations in molar ratio 1:1 or 2:1 (M:L) to yield either mono- or binuclear complexes, respectively. The ligand and its metal complexes were characterized by elemental analyses, IR, (1)H NMR, Mass, and UV-Visible spectra and the magnetic moments and electrical conductance of the complexes were also determined. For binuclear complexes, the magnetic moments are quite low compared to the calculated value for two metal ions complexes and this shows antiferromagnetic interactions between the two adjacent metal ions. The ligand and its metal complexes were tested against a Gram + ve bacteria (Staphylococcus aureus), a Gram -ve bacteria (Escherichia coli), and a fungi (Candida albicans). The tested compounds exhibited high antibacterial activities.     

Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions

The effects of gold(I) complexes (auranofin, triethylphosphine gold and aurothiomalate), gold(III) complexes ([Au(2,2'-diethylendiamine)Cl]Cl(2), [(Au(2-(1,1-dimethylbenzyl)-pyridine) (CH(3)COO)(2)], [Au(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)(OH)](PF(6)), [Au(bipy(dmb)-H)(2,6-xylidine)](PF(6))), metal ions (zinc and cadmium acetate) and metal complexes (cisplatin, zinc pyrithione and tributyltin) on mitochondrial thioredoxin reductase and mitochondrial functions have been examined. Both gold(I) and gold(III) complexes are extremely efficient inhibitors of thioredoxin reductase showing IC(50) ranging from 0.020 to 1.42 microM while metal ions and complexes not containing gold are less effective, exhibiting IC(50) going from 11.8 to 76.0 microM. At variance with thioredoxin reductase, auranofin is completely ineffective in inhibiting glutathione peroxidase and glutathione reductase, while gold(III) compounds show some effect on glutathione peroxidase. The mitochondrial respiratory chain is scarcely affected by gold compounds while the other metal complexes and metal ions, in particular zinc ion and zinc pyrithione, show a more marked inhibitory effect that is reflected on a rapid induction of membrane potential decrease that precedes swelling. Therefore, differently from gold compounds, the various metal ions and metal complexes exert their effect on different targets indicating a lower specificity. It is concluded that gold compounds are highly specific inhibitors of mitochondrial thioredoxin reductase and this action influences other functions such as membrane permeability properties. Metal ions and metal complexes markedly inhibit the activity of thioredoxin reductase although to an extent lower than that of gold compounds. They also inhibit mitochondrial respiration, decrease membrane potential and, finally, induce swelling.     

Antibacterial activity of ZnO nanoparticle suspensions on a broad spectrum of microorganisms

Nanoparticle metal oxides represent a new class of important materials that are increasingly being developed for use in research and health-related applications. Highly ionic metal oxides are interesting not only for their wide variety of physical and chemical properties but also for their antibacterial activity. Although the in vitro antibacterial activity and efficacy of regular zinc oxides have been investigated, little is known about the antibacterial activity of nanoparticles of ZnO. Preliminary growth analysis data suggest that nanoparticles of ZnO have significantly higher antibacterial effects on Staphylococcus aureus than do five other metal oxide nanoparticles. In addition, studies have clearly demonstrated that ZnO nanoparticles have a wide range of antibacterial effects on a number of other microorganisms. The antibacterial activity of ZnO may be dependent on the size and the presence of normal visible light. The data suggest that ZnO nanoparticles have a potential application as a bacteriostatic agent in visible light and may have future applications in the development of derivative agents to control the spread and infection of a variety of bacterial strains.     

Platinum(II) complexes with fluoroquinolones: Synthesis and characterization of unusual metal-piperazine chelates

The fluoroquinolones constitute an important class of synthetic antimicrobial agents. The interaction between these compounds and metallic cations has been investigated primarily with the goal of identifying the functional groups directly linked to the metal. Furthermore, there has been some additional work investigating the effect of metal ions upon antibacterial activity. The vast majority of the metallic complexes reported in the literature show coordination of the fluoroquinolone through the carboxylate and the carbonyl oxygen atoms. In this work, we report the synthesis and characterization of platinum(II) complexes with ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin, and gatifloxacin. The resulting complexes present the fluoroquinolone coordinated through the nitrogen atoms of the piperazine ring, which is unusual. The proposed structures were supported by spectroscopic evidence (IR, NMR, and mass spectra) as well as by theoretical studies.     

In-vitro antibacterial and cytotoxic activity of cobalt (ii), copper (ii), nickel (ii) and zinc (ii) complexes of the antibiotic drug cephalothin (Keflin)

Keflin (kefl) interacts with Co(II), Cu(II), Ni(II) and Zn(II) metal ions leading to complexes of the type M(kefl)2Cl2 and M(kefl)Cl2, which have been characterized by physicochemical and spectroscopic methods. Magnetic moment, IR, electronic spectral and elemental analyses data suggest that keflin behaves tridentately forming octahedral or trigonal bipyramidal complexes with the metal ions mentioned above. The new compounds have been screened in-vitro for antibacterial and cytotoxic activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi, Shigella dysentriae, Bacillus cereus, Corynebacterium diphtheriae, Staphylococcus aureus and Streptococcus pyogenes bacterial strains. Compounds, 4 and 8 showed promising activity (90%) against seven, compound 6 showed significant activity (52%) against four and, compounds 1 and 5 showed activity (40%) against three test bacterial strains at concentration of 10 microM.     

Antibacterial and Antifugal Mono- and Di-substituted Symmetrical and Unsymmetrical Triazine-derived Schiff-bases and their Transition Metal Complexes

A new series of antibacterial and antifungal triazine-derived mono- and di-substituted (symmetrical and unsymmetrical) Schiff-bases and their cobalt(II), copper(II), nickel(II) and zinc(II) metal complexes have been synthesized and characterized by their elemental analyses, molar conductances, magnetic moments and IR and electronic spectral measurements. IR spectra indicated the ligands to act as tridentate towards divalent metal ions via a trazine-N, the azomethine-N and, indole-NH and deprotonated-O of salicylaldehyde. The magnetic moments and electronic spectral data suggest octahedral geometry for the Co(II), Ni(II) and Zn(II)complexes and square-pyramid for Cu(II) complexes. NMR spectral data of the ligands and their diamagnetic zinc(II) complexes well-define their proposed structures/geometries. Elemental analyses data of the ligands and metal complexes agree with their proposed structures/geometries. The synthesized ligands, along with their metal complexes were screened for their 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. The results of these studies show the metal complexes to be more antibacterial/antifungal against two or more species as compared to the uncomplexed Schiff-base ligands.