Synthesis, antibacterial and antifungal activity of some new pyridazinone metal complexes

The new various metal complexes of 5-benzoyl-4-hydroxy-2-methyl-6-phenyl-2H-pyridazin-3-one were synthesized. All the complexes were evaluated for their antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi using microdilution procedure. The Cd(II) and Ni(II) complexes exhibited selective and effective activities against one Gram-positive bacterium (Staphylococcus aureus ATCC 6538), one Gram-negative bacterium (Pseudomonas putida ATCC 12633) and against two yeast (Candida albicans ATCC 27541 and Candida tropicalis 1828) in contrast to poor activity observed other microorganisms. The new synthesized complexes were characterized using IR, 1H-NMR and UV spectral data together with elemental analysis.     

Synthesis, spectral characterization, in vitro antibacterial, antifungal and cytotoxic activities of Co(II), Ni(II) and Cu(II) complexes with 1,2,4-triazole Schiff bases

A series of metal complexes of cobalt(II), nickel(II) and copper(II) have been synthesized with newly synthesized biologically active 1,2,4-triazole Schiff bases derived from the condensation of 3-substituted-4-amino-5-mercapto-1,2,4-triazole and 8-formyl-7-hydroxy-4-methylcoumarin, which have been characterized by elemental analyses, spectroscopic measurements (IR, UV-vis, fluorescence, ESR), magnetic measurements and thermal studies. Electrochemical study of the complexes is also reported. All the complexes are soluble to limited extent in common organic solvents but soluble to larger extent in DMF and DMSO and are non-electrolytes in DMF and DMSO. All these Schiff bases and their complexes have also been screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa and Salmonella typhi) and antifungal activities (Aspergillus niger, Aspergillus flavus and Cladosporium) by MIC method. The brine shrimp bioassay was also carried out to study their in vitro cytotoxic properties.     

Synthesis, characterization, cytotoxicity, antibacterial and antifungal evaluation of some new platinum (IV) and palladium (II) complexes of thiodiamines

Some new platinum (IV) and palladium (II) thiodiamine complexes of type [Pt(L)2Cl2] and [Pd(L)Cl2], [where, L=(cyclohexyl-N-thio)-1,2-ethylenediamine (L(1)) and (cyclohexyl-N-thio)-1,3-propanediamine (L(2))] have been synthesized. The thiodiamines coordinate as a bidentate N-S ligand. The synthesized platinum (IV) and palladium (II) complexes of the thiodiamines were characterized by elemental analysis, IR, mass, electronic and (1)H NMR spectroscopic studies. These complexes were also screened for cytotoxicity, in vitro antifungal and in vitro antibacterial activities. Thermodynamic parameters such as activation energy (Ea), apparent activation entropy (S(#)) and enthalpy change (DeltaH) for the dehydration and decomposition reactions of one complex has also been evaluated.     

Synthesis, antibacterial and antifungal activity of some new thiazolylhydrazone derivatives containing 3-substituted cyclobutane ring

A series of Schiff bases, combining 2,4-disubstituted thiazole and cyclobutane rings, and hydrazone moieties in the same molecule, was synthesized, characterized and evaluated for screening antibacterial and antifungal activities on microorganisms, respectively, on four bacteria and Candida tropicalis. The structures of original compounds were confirmed by analytical and spectroscopic (FT-IR, (1)H NMR and (13)C NMR) methods and elemental analysis. Both the antibacterial and antifungal activities and MIC values of compounds were reported. Among the tested compounds, the most effective compound providing a MIC value of 16 microg ml(-1) are 2 against C. tropicalis and Bacillus subtilis and 3 against B. subtilis only.     

Synthesis,cytotoxic activity on MCF-7 cell line and mutagenic activity of platinum(II) complexes with 2-substituted benzimidazole ligands

Four Pt(II) complexes with 2-H/or-methyl/or-aminomethylbenzimidazole or 1,2-dimethylbenzimidazole ligands as "non-leaving groups" were synthesized and their antiproliferative properties were tested against the human MCF-7 breast cancer cell line. The mutagenic potentials of the complexes were tested in Salmonella typhimurium strains TA 98 and TA 100 in the absence of S9 rat liver fraction. In general, Pt(II) complexes tested which were found to be less active than cisplatin, exhibited moderate in vitro cytotoxic activity on MCF-7 cell line. Among the complexes tested, Pt(II) complex with 2-aminomethylbenzimidazole ligand was found to be highly mutagenic in S. typhimurium TA 98 and low mutagenic in S. typhimurium TA 100. Pt(II) complex with 1,2-dimethylbenzimidazole was mutagenic only in S. typhimurium TA 98. The other two complexes were found to be non-mutagen in both strains.     

Synthesis, physicochemical properties and antimicrobial activity of some new benzimidazole derivatives

Some derivatives of benzimidazole were synthesized by nucleophilic substitution of 2-substituted-1H-benzimidazole. The resulting ethyl (2-substituted-1H-benzimidazol-1-yl) acetate on treatment with hydrazine hydrate yielded 2-(2-substituted-1H-benzimidazol-1-yl) acetohydrazide, which on further reaction with one equivalent of different aliphatic or aromatic carboxylic acids in the presence of phosphoryl chloride afforded the corresponding target compounds, 2-substituted-1-[{(5-substituted alkyl/aryl)-1,3,4-oxadiazol-2-yl} methyl]-1H-benzimidazole. The structures of the synthesized compounds were evaluated by spectral and elemental methods of analyses. All the synthesized compounds were screened for their antimicrobial activities. All of the derivatives showed good activity towards Gram-positive bacteria and negligible activity towards Gram-negative bacteria. Some of the synthesized compounds showed moderate activity against tested fungi.     

Synthesis, characterization and biological studies of Co(II), Ni(II), Cu(II) and Zn(II) complexes with bidentate Schiff bases derived by heterocyclic ketone

A series of metal complexes of Co(II), Ni(II), Cu(II) and Zn(II) have been synthesized with newly prepared biologically active ligands. These ligands were prepared by the condensation of 4-amino-5-mercapto-3-methyl-s-triazole (AMMT), 4-Amino-3-ethyl-5-mercapto-s-triazole (AEMT) with 2-acetylpyridine. The structure of the complexes have been proposed by elemental analyses, spectroscopic data i.e. IR, 1H NMR, electronic and magnetic measurements. Thermal studies of the complexes are also reported. Antibacterial activities of 10 complexes have been studied in vitro. Heterocyclic bidentate Schiff bases were associated with substantially higher antibacterial activities than some commercial antibiotics.     

Synthesis and in vitro cysticidal activity of new benzimidazole derivatives

Despite albendazole being the drug of choice in neurocysticercosis treatment, its low solubility limits its bioavailability; therefore, more research is required in order to find new molecules with cestocidal activity and adequate aqueous solubility. A set of 13 benzimidazole derivatives were synthesized and their in vitro activities were evaluated against Taenia crassiceps cysts, using albendazole sulfoxide as reference molecule, showing that two of them exhibited good activity. Molecular modelling revealed that the cysticidal efficacy depends on the presence on the molecule of an H in the 1-position, a planar carbamate group at 2-position, and if the substituent in 5-position is voluminous, it should be orthogonal to the benzimidazole ring.     

Synthesis,physicochemical investigation and cytotoxic activity of new Pt(II) complexes with hydantoin ligands

The interaction of cis-dichlorodiaminplatinum(II) (cis-DDP) with 2,4-imidazolidenedione-5-methyl-5-phenyl was studied. The method of preparation of the new Pt(II) complex consisted in precipitation of chloride ions from cis-DDP via a diaqua complex and reaction with the ligand in water-organic media. On the basis of IR spectra, (1)H- and (13)C-NMR analysis the coordination mode of the ligand and most fitting structures of two isomeric complexes were proposed. The pharmacological investigations revealed that the new Pt(II) complex with 5-methyl-5-phenylhydantoin (PtMPH) as well as the previously described Pt(II) complexes with cyclopentanespiro-5'-hydantoin and cyclohexanespiro-5'-hydantoin (PtCHH) exerted concentration-dependent cytotoxic effect in a panel of human tumor cell lines. On the basis of the IC(50) values obtained PtMPH proved to be the most active cytotoxic agent. The other investigated complexes were less active, and among them PtCHH was the least potent antineoplastic agent. The pharmacodynamic investigation of PtMPH showed that this compound induces programmed cell death (apoptosis), as evidenced by the detection of oligonucleosomal DNA fragmentation in HL-60 cells after treatment with PtMPH.     

Synthesis, spectroscopic characterization and antibacterial activity of new cobalt(II) complexes of unsymmetrical tetradentate (OSN2) Schiff base ligands

Cobalt ion complexes with the Schiff bases, (4-X-2-{[2-(2-pyridine-2-yl-ethylsulfanyl)ethylimino]methyl}phenol (X = methoxy (OMe), phenylazo (N₂Ph), bromo (Br), nitro (NO₂)),were synthesized and investigated by several techniques using elemental analysis (C, H, N), FTIR, electronic spectra and molar conductivity. The thermal stability of free ligands and related cobalt complexes were studied by using differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). Cyclic voltammetry indicates that the investigated cobalt complexes, under the experimental conditions, have irreversible redox behavior. The synthesized compounds have antibacterial activity against the four Gram-positive bacteria: Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus and Bacillus anthracis and also against the two Gram-negative bacteria: Klebsiella pneumoniae and Pseudomonas aeruginosa. The activity data show that the parent Schiff bases are more potent antibacterials than the cobalt complexes.     

Synthesis, characterization and antibacterial activity of cobalt(III) complexes with pyridine-amide ligands

The ligands 2-(N-(X-pyridyl)carbamoyl)pyridine (X=2, 3 or 4 for HL1-HL3, respectively) and 2,6-bis(N-(Y-pyridyl)carbamoyl)pyridine (Y=2, 3 or 4 for H2L4-H2L6, respectively) in their mono- and di-deprotonated forms have been used to synthesize kinetically stable cobalt(III) compounds [Co(L1-3)3] (1-3) and Na[Co(L4-6)2] (4-6), respectively. The Co(III) ion is in octahedral environment and is surrounded by three bidentate ligands in complexes 1-3 and two tridentate ligands in complexes 4-6. Ligands coordinate the cobalt center via amidic-N and pyridine-N centers forming a 5-membered chelate ring. Complexes 1-6 have thoroughly been characterized by the various spectroscopic analyses (1H NMR, 13C NMR, UV-vis, IR, mass), elemental analysis, and conductivity measurement. All complexes have been assayed for in vitro antimicrobial activity against clinically isolated resistant strains of Pseudomonas, Proteus, Escherichia coli and standard strains of Pseudomonas aeruginosa (MTCC 1688), Shigella flexneri (MTCC 1457), Klebsiella planticola (MTCC 2272). All cobalt compounds show mild to moderate activity. However, complexes [Co(L1)3] (1) and Na[Co(L4)2] (4) were found to have potent activity against standard and pathogenic resistant bacteria used in the study. Their MIC ranged from 2.7 to 187 microg/ml. In vitro toxicity tests demonstrated that all complexes were less cytotoxic than that of gentamycin on HEK cell lines and the results reveal that these complexes can act as potent antimicrobial agents.     

Co(III), Ni(II), Zn(II) and Cd(II) complexes with 2-acetyl-2-thiazoline thiosemicarbazone: Synthesis, characterization, X-ray structures and antibacterial activity

The new ligand 2-acetyl-2-thiazoline thiosemicarbazone (HATtsc) and the complexes [Co(ATtsc)₂]₂[CoCl₄]·2H₂O (1), [Co(ATtsc)₂]NO₃·H₂O (2), [Ni(HATtsc)₂](NO₃)₂ (3), [ZnCl₂(HATtsc)]·CH₃CN (4), [{CdCl(HATtsc)}₂(μ-Cl)₂]·2H₂O (5) and [{Cd(NO₃)(HATtsc)}₂(μ-NO₃)₂] (6) were isolated and characterized by a variety of physico-chemical techniques and X-ray diffraction. The structure of HATtsc in 1 and 2 presented a thiolate form while in 3-6 the thione form was present, as it was in free ligand. In addition, we studied the antibacterial activity of the ligand and complexes 2-6 against some representative bacteria. Cd(II) complexes were more active against Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Bacillus subtilis than organic ligand. Conversely, Cd(II) compounds seemed to interfere in the cell separation of B. subtilis.     

Synthesis, characterization and antitumor activity of new type binuclear platinum(II) complexes

Five new type binuclear platinum(II) complexes (a-e) have been synthesized and characterized by elemental analysis, conductivity, thermal analysis, IR, UV, (1)H NMR and mass spectral techniques. The cytotoxicity of the complexes was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. The acute toxicity and antitumor activity of complex ein vivo were also studied. The results indicate that complexes a-d have no activity against HL-60, MCF-7, BGC-823, EJ and HCT-8 cell lines, with a higher IC(50) value (>50 microM). Complex e confers substantially greater cytotoxicity against HL-60, MCF-7, BGC-823, EJ and HCT-8 cell lines with an IC(50) value of 0.02+/-0.009, 1.70+/-0.21, 4.00+/-0.35, 0.98+/-0.02 and 1.02+/-0.21 microM, respectively. LD(50) of complex e is 815.3mg/kg, it was significantly higher than that of cisplatin and carboplatin. Complex e at dose of 4, 12 and 20mg/kg has no activity against mouse hepatocarcinoma H22 and Lewis lung carcinoma in mice, but displays significant activity against human ovarian carcinoma A2780 and human colon carcinoma HCT-116 in nude mice at dose of 12 mg/kg, and activity is similar to that of cisplatin at dose of 4 mg/kg. Complex e at dose of 20mg/kg has no activity against human lung adenocarcinoma A549 in nude mice (P>0.05). The results suggest that the species of amine for the new type binuclear platinum complexes have important effect on their cytotoxicity, and they may be a new class platinum anticancer drugs.     

Synthesis of 3-acetoxyazetidin-2-ones and 3-hydroxyazetidin-2-ones with antifungal and antibacterial activity

The synthesis of a series of 3-acetoxyazetidin-2-ones 3a–n and 3-hydroxyazetidin-2-ones 6a–j is reported together with the antibacterial and antifungal evaluation of these compounds. An additional series of 3-acetoxyazetidin-2-ones 11a–h which possess a free carboxylic acid group on the N-1 aryl ring were obtained by treatment of suitably substituted Schiff bases 10a–h with acetoxyacetyl chloride. The novel bicyclic structures 7-acetoxy-6-phenyl-5-thia-1-azabicyclo[4.2.0]octan-8-one 13 and 7-hydroxy-6-phenyl-5-thia-1-azabicyclo[4.2.0]octan-8-one 14 were also obtained. Many of the compounds displayed antifungal activity in vitro when evaluated against the pathogenic fungi Cryptococcus neoformans, Candida albicans, Candida tropicalis, Candida parapsilosis, Candida glabrata, and Trichosporon cutaneum, while 3-acetoxyazetidin-2-ones 11a–h containing a free carboxylic acid group on the N-1 aryl ring displayed antibacterial activity against Staphylococcus aureus, Proteus vulgaris, Pseudomonas aeruginosa, Bacillus subtilis, Klebsiella aerogenes and Escherischia coli.     

Synthesis and crystal structure of two new dinuclear cobalt(II) complexes interaction with HeLa cells

Two novel dinuclear complexes [Co₂(L)₂(phen)₂·2H₂O]_n (1), [Co₂(L)₂(bipy)₂]_n (2) (where phen = 1,10-phenanthroline, bipy = 2,2′-bipyridine, and L = biphenyl-2,4′-dicarboxylic acid) have been synthesized and characterized using IR, ¹H NMR, element analysis and single-crystal X-ray diffractometry. The binding of the complexes with HC-DNA (HeLa cells DNA, which was extracted by ourselves) was investigated by fluorescence spectrum. The experimental results show that the two complexes have the ability to bind with extracted HC-DNA. Gel electrophoresis assay demonstrates the ability of the complexes to cleave the extracted HC-DNA. The complexes exhibit a higher cytotoxicity against tumor cells as against normal cells in vitro. Further more, the apoptotic tests indicate that the complexes have an apoptotic effect on HeLa cells.     

Synthesis and characterization of the Zn(II) and Cu(II) piperidinyl isoeuxanthone complexes: DNA-binding and cytotoxic activity

Two new complexes ZnL₂·2H₂O (1) and CuL₂·2H₂O (2) (HL = 1-hydroxy-6-(2-(1-piperidinyl)ethoxy)xanthone) have been synthesized and characterized. Their interactions with calf thymus DNA (ct DNA) were investigated by absorption spectroscopy, fluorescence spectroscopy, ethidium bromide (EB) displacement experiments, circular dichroism spectroscopy and viscosity measurements. Experimental results suggested that there were intercalative interactions of the complexes with DNA. The binding affinity of complex 2 was higher than that of 1. In addition, the cytotoxic effects of both complexes were evaluated with lung adenocarcinoma (GLC-82), esophagus squamous cancer (ECA109) and human gastric cancer (SGC7901) cells using MTT assay. Both were potent exhibiting significant cytotoxicity in vitro.     

Synthesis, antibacterial, antifungal and anti-HIV activities of norfloxacin mannich bases

Mannich bases of norfloxacin were synthesized by reacting them with formaldehyde and several isatin derivatives. Their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analysis. Investigation of in vitro antimicrobial activity of compounds was done by the agar dilution method against 28 pathogenic bacteria, eight pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. The in vivo antibacterial efficacy of selected derivatives was determined using a mouse infection model. All the synthesized compounds are more active than norfloxacin against the 13 bacteria tested. The compounds are also more active than the standard drug clotrimazole against Histoplasma capsulatum. Two compounds S-8 and S-9 have shown inhibition against HIV-1 (III B) with EC(50) values of 11.3 and 13.9 microgram/mL, respectively. In the mouse protection test, two compounds S-4 (ED(50): 1.25 mg/kg) and S-9 (ED(50): 1.62 mg/kg) are more active than norfloxacin (ED(50): 6mg/kg). Among the compounds tested, 1-ethyl-6-fluoro-1, 4-dihydro-4-oxo-7[[N(4)-[5'-bromo-3'-(4'-amino-5'-trimethoxybenzylpyr imidin-2'-yl]-imino-1'-isatinyl]methyl]N(1)-piperazinyl]-3-q uinoline carboxylicacid (S-9) showed promising activity in all the three tests.     

Synthesis, characterization and antimicrobial activity of Co(II), Zn(II) and Cd(II) complexes with N-benzyloxycarbonyl-S-phenylalanine

In this paper the first complexes of M(2+) ions (M(2+) = Zn(2+), Cd(2+) and Co(2+)) with N-benzyloxycarbonyl-S-phenylalaninato ligand (1-3) are described. The new complexes were characterized by means of elemental analysis, IR and UV-vis spectroscopy, molar conductivity measurements and (1)H, (13)C and (15)N NMR spectroscopy (1D and 2D). The Co(II) complex adopts an octahedral geometry, and the Zn(II) and Cd(II) complexes adopt a tetrahedral one. For the first time, the antimicrobial activity of N-benzyloxycarbonyl-S-phenylalaninato ligand (N-Boc-S-phe) and the complexes 1-3 was investigated against gram-positive: Micrococcus luteus, Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Bacillus subtilis and gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and two strains of the yeast Candida albicans. It was shown that the complexes were effective against most strains. The best activity was detected against the yeast C. albicans.     

Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles

A series of novel actinonin derivatives containing a benzimidazole heterocycle linked as amide isostere have been designed and synthesized. The structures of all the synthesized compounds were confirmed by analytical and spectroscopic methods. All the compounds were evaluated in vitro against Staphylococcus aureus, Klebsiella pneumoniae, and Sarcina lutea. Among them, compound 1a with unsubstituted benzimidazole ring exhibited potent antibacterial activities.     

Synthesis and studies on some new fluorine containing triazolothiadiazines as possible antibacterial, antifungal and anticancer agents

Synthesis of a series of 7-arylidene-6-(2,4-dichlorophenyl)-3-aryloxymethyl/anilinomethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) by the condensation of 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-propen-1-one (1) and 4-amino-5-mercapto-3-aryloxymethyl/anilinomethyl-1,2,4-triazoles (2) is described. The newly synthesized compounds were characterized by elemental analysis IR, 1H NMR and mass spectral data. These compounds were tested for their antimicrobial activities against Escherichia coli, Staphylococcus aureus (Smith), Psuedomonas aeruginosa (Gessard), Bacillus subtilis and Candida albicans. Some of the newly synthesized compounds were also screened for their anticancer activity. Among them compounds 3m, 3o, 3q showed in vitro anticancer activity.