An efficient and simple protocol for the synthesis of a new class of diverse bis(indolyl)pyridines analogues of the marine alkaloid nortopsentin has been reported. A one-pot four-component condensation of 3-cyanocarbomethylindole, various aldehyde, 3-acetylindole, and ammonium acetate in glacial acetic acid led to the formation of 2,6-bis(1H-indol-3-yl)-4-(substituted-phenyl)pyridine-5-carbonitriles. Additionally, 2,6-bis(1H-indol-3-yl)-4-(benzofuran) pyridine-5-carbonitriles were prepared via a one-pot four-component condensation of 3-cyanocarbomethylindole, various N-substituted-indole-3-aldehydes, 2-acetylbenzofuran, and ammonium acetate. The synthesized compounds were evaluated for their ability to inhibit biofilm formation against the Gram-positive bacterial reference strains Staphylococcus aureus ATCC 6538 and the Gram-negative strain Escherichia coli ATCC 25922. Some of the new compounds showed a marked selectivity against the Gram-positive and Gram-negative strains. Remarkably, five compounds 4b, 7a, 7c, 7d and 8e demonstrated good antibiofilm formation against S. aureus and E. coli. On the other hand, the release of reducing sugars and proteins from the treated bacterial strains over the untreated strains was considered to explain the disruption effect of the selected compound on the contact cells of S. aureus and E. coli. Out of all studied compounds, the binding energies and binding mode of bis-indole derivatives 7c and 7d were theoretically the best thymidylate kinase, DNA gyrase B and DNA topoisomerase IV subunit B inhibitors.

Synthesis, structural characterization, density functional theory (B3LYP) calculations, thermal behaviour, docking and antimicrobial activity of 4-amino-5-(heptadec-8-en-1-yl)-4H-1,2,4-triazole-3-thiol and its metal chelatesThe structure of prepared triazole ligand 4-amino-5-(heptadec-8-en-1-yl)-4H-1,2,4-triazole-3-thiol and its coordination behaviour towards transition metal ions Ni (II), Co (II), Fe (III), Cd (II) and Cu (II) have been studied using magnetic measurements, elemental analyses and electronic, Fourier transform infrared and 1 H NMR spectroscopies. The thermal behaviours of the triazole ligand and its chelates were investigated and their thermal decomposition possibilities are proposed. The stages of all thermal decompositions are discussed.The Gaussian09 program was used to optimize the structural formula for the triazole ligand. Applying the DFT/B3LYP/6-311 basis set method, important theoretical parameters were calculated. The target triazole and its metal chelates were investigated in vitro against Escherichia coli, Staphylococcus aurous, Aspergillus flavus and Candida albicans, and were found to exhibit good antimicrobial activity. These results were confirmed using theoretical molecular docking.

No abstract

Synthesis of various heterocycles having fatty acid residues is described using ethyl-4-(hexadec-7-enyl)-3-oxobutanoate as starting material by reaction with different reagents. Preliminary antibacterial testing showed that the compounds ethyl-4-(hexadec-7-enyl)-3-oxobutanoate and 3-[octadec-9-ene-1-one]-chromen-2-one are the most promising.A search in the literature showed that heterocycles containing oleoyl residues possess bacteriocidal activity. 1,2 Oil wastes obtained from refinery factories are a big problem in Egypt and in an attempt to make use of these wastes, we try in this investigation to use oleic acid separated from the waste as a starting material to prepare some new heterocycles with anticipated bacteriocidal activity. [3][4][5] With this aim oleoyl chloride 1 was used to acylate Meldrum ' s acid) in the presence of pyridine. The resulting acylated Meldrum ' s acid 3 was subjected to an acidic aqueous work up, and immediately thereafter refluxed in absolute ethanol 6 to give the b-keto ester 4 in good yield (cf. Scheme 1). The 1 H NMR spectrum of ethyl-4-(hexadec-7-enyl)-3oxobutanoate 4 revealed the active methylene group at d = 3.35 ppm, and moreover the 13 C NMR showed signals at 202.36 and 166.87 ppm, attributed to the two carbonyl groups.Compound 4 was reacted with N,N-dimethyl formamide dimethylacetal as a one-carbon synthon to yield the 3-dimethylamino propenoate derivative 5. In the 1 H NMR spectrum there appears a new broad signal at d = 2.96 ppm characteristic of the dimethylamino group along with the methine-H at 7.59 ppm. Additionally, the mass spectrum of 5 reveals a molecular ion peak at m/z = 408 corresponding to the molecular formula C 25 H 45 NO 3 .Enamine 5, reacts with phenylhydrazine in acetic acid giving pyrazole-3-one derivative 6. The mass spectrum of 6 gave a molecular ion peak at m/z = 424 which was in accordance with the proposed molecular weight.Continuing our investigation, the b-keto ester 4 was allowed to react with thiourea in the presence of sodium ethoxide to give the uracil derivative 7 having the fatty residue at position 6 (cf. Scheme 2). The 1 H NMR of 7 showed a new exchangeable broad signal at d = 12.34 characteristic for the uracil NH protons, 7 in addition to the uracil H-5 at 5.70 ppm, while its MS is in accord with the molecular formula C 21 H 37 N 2 OS (m/z = 366).

Mononuclear chelates of Ni(II), Co(II), Fe(III), Cd(II), and Cu(II) derived from triazole novel tridentate ligands were prepared and characterized by different spectroscopic methods. The metal to ligand ratio was 1 : 2, which was revealed by elemental analysis. All the complexes were electrolytic in nature as suggested by the conductivity measurements. IR pointed out that the coordination of the triazole ligand toward the metal ions was carried out through N amino and S thiophenolic atoms. The complexes were found to have octahedral geometry, and their thermal stability was also studied. The XRD spectrum of Co(II) and Fe(III) complexes concluded their crystalline structure. The parent ligand and its chelates were investigated for antimicrobial potential. Bioassay of all triazole complexes showed increased activity as compared to that of the ligand. The complexes having Ni(II), Co(II), and Cu(II) ions as metal center exhibited superior antibacterial activity in opposition to Gram-positive (B. subtilis and S. pyogenes) and Gram-negative (E. coli and P. vulgaris) bacterium as compared to standard.