Synthesis, Biological Profile, and Molecular Docking of Some New BisImidazole Fused Templates and Investigation of Their Cytotoxic Potential as Anti-tubercular and/or Anticancer Prototypes

Background: There is a great need to discover more drugs with antimycobacterial activities to fight lung cancer and tuberculosis (two of the deadliest diseases world-wide). To our knowledge, the present study is the first to report antimycobacterial activity of imidazole-fused heterocycles. Objective: Construction of some bis-imidazole fused heterocycles with potential anti-tubercular and/or potent antitumor activities. Method: A series of bis-imidazole fused derivatives 6-8 and 13-16 was constructed using bis-phenacyl bromide derivative 2 as a synthetic platform. Compound 2 was also used to access bis-quinoxaline 20, bis-benzothiazine derivatives 23, and bisthiazolopyrimidine derivatives 26. The new bis-imidazole derivatives were evaluated for their anticancer activity against lung carcinoma cell line (A-549) using Cisplatin as a reference drug. The new compounds were also screened for their antitubercular activity against M. tuberculosis (ATCC 25177) using Isoniazid as a reference drug. Result: Among the new bis-imidazole derivatives, three examples showed remarkable antitumor activities while five other compounds showed high antimycobacterial activity. Conclusion: A novel series of bis-imidazole fused heterocycles was developed. Multiple prototypes of this new series showed remarkable anti-tubercular and/or potent antitumor activities.

3-(Pyridin-4-yl)acetylacetone: a donor ligand towards mercury(II) halides and a versatile linker for complex materials

The ditopic organic molecule 3-(pyridin-4-yl)acetylacetone (HacacPy) acts as a pyridine-type ligand towards HgX2(X= Cl, Br, I). The nature of the anion and the ligand-to-cation ratio dominate the outcome of the reaction. Two different coordination compounds form with HgCl2, namely a ligand-rich mononuclear complex, HgCl2(HacacPy)2, and a ligand-deficient one-dimensional chain polymer, [Hg(μ-Cl)2(HacacPy)]1∞, with five-coordinated HgIIcations. Two compounds are also observed for HgBr2, a molecular complex isomorphous to the chloride derivative and a chain polymer with the composition [Hg(μ-Br)Br(HacacPy)]1∞, in which the cations are four-coordinated. The ligand-rich mononuclear and ligand-deficient polymeric chloride and bromide complexes may be interconvertedviathermal degradation and mechanochemical synthesis. In contrast to the chloride and bromide compounds, the reaction product with HgI2does not depend on the ligand-to-cation ratio but corresponds to [Hg(μ-I)I(HacacPy)]1∞, isomorphous to the bromide derivative. TheN-coordinated HacacPy complexes could not be deprotonated and further crosslinked with a second cation. Synthesis of mixed-metal products could be achieved, however, by deprotonation of the acetylacetone moiety in HacacPy and formation of tris-chelated Fe(acacPy)3and Al(acacPy)3complexes in the first step. These mononuclear building blocks act as bridging poly(pyridine) ligands towards HgIIhalides and form two structure types. The first represents a one-dimensional ladder, with the tris(ligand) complexes acting as triconnected nodes and the HgIIhalides acting as linkers. In the alternative unprecedented product, both the tris(ligand) complexes and the [HgX2(μ-X)HgX] groups act as equivalent triconnected nodes. They form a uninodal two-dimensional coordination network with vertex symbol 4.82andfestopology.

A STUDY OF THE SYNTHESIS OF VERATRYL CYANIDE REQUIRED AS AN INTERMEDIATE FOR THE PREPARATION OF C-9154 ANTIBIOTIC DERIVATIVE FROM VANILIN

The synthesis of veratryl cyanide [1-(3,4-dimethoxy phenyl acetonitril] required as an intermediate for the preparation of C-9154 antibiotic derivative was carried out. The starting material used was vanilin, while the reaction steps consisted of (1) methylation of vanilin, (2) reduction of veratraldehyde, (3) synthesis of veratryl bromide, and (4) treatment of this bromide with KCN. The analysis of the products was carried out using IR, 1H NMR and GC-MS spectrophotometers. The methylation of vanilin was conducted using dimethylsulfate and NaOH at 100 oC for 2 hours to give 79.3% yield of veratraldehyde. The reduction of veratraldehyde with LiBH4 in ethanol - THF mixture (1:1 v/v) at reflux for 4 hours afforded veratryl alcohol in 85.3% yield. This veratryl alcohol was treated with red phosphorous and Br2 in CCl4 at 60 oC for 2 hours to give 1-(2-bromo-4,5-dimethoxy)-phenyl bromomethane in 67.4% yield, instead of the desired veratryl bromide [1-3,4-dimethoxy)-phenyl bromomethane]. This benzyl bromide derivative was then treated with KCN in the presence of tween 80 as a phase catalyst transsfer in benzene-water solvent system at reflux for 2 hours to yield 1-(2-bromo-4,5-dimethoxy)phenyl acetonitril in 58.5%. Keywords: Vanilin, veratryl cyanide, C-9154 antibiotic derivative

High-spin Cyclopentadienyl Complexes, Part 7. Ambivalent Interpretation of the Bonding in Iron-Copper Complexes: Metalated Arene versus Carbocyclic Carbene

The electron distribution within a mesityl ligand bridging a cyclopentadienyliron fragment attached to the mesityl π system and a second metal fragment connected to the ipso carbon of the mesityl ring has been probed using a copper(I) halide as a component in [CpmFe (μ,η5 :η1-C6H2Me3)CuCl] (2) and its copper bromide derivative 3. This approach minimizes steric effects and allows for DFT calculations the results of which are in very good agreement with structural data. The calculations show a significant carbene character already for the bare phenyl anion as a result of electrostatic repulsion of the lone pair pushing the π electrons away from the ipso carbon towards the para carbon atom of the aromatic ring. π Coordination of a cyclopentadienyliron(II) fragment to the phenyl anion to form a hypothetical sandwich complex does not change this situation. The iron center rather follows the unsymmetric distribution of π charge with an unsymmetrical coordination to the π system. Coordination of a copper(I) chloride moiety to the phenyl anion or to the hypothetical π complex [CpFe(C6H5)] in both cases equally lowers that carbene character by attracting the lone pair of the ipso carbon and thus decreasing its repulsive influence on the π electrons.