A zinc(II) amidine complex: tandem synthesis,structure, and self assembly

A five-coordinate zinc(II) amidine complex, [Zn(DEP)(N₃)₂] (DEP = N′-(2-(diethylamino)ethyl)picolinamidine), has been synthesized with 2-cyanopyridine and sodium azide in the presence of zinc(II) acetate dihydrate. The structure of the complex is confirmed by single-crystal X-ray diffraction analysis. The complex crystallizes in triclinic space group P-1 with cell dimensions a = 7.486(5) Å, b = 7.678(5) Å, c = 14.480(5) Å, α?=?96.697(5)°, β = 90.282(5)°, and γ?=?95.716(5)°. The hydrogen bonding interactions in the complex lead to the formation of a 2-D supramolecular network. The complex shows fluorescence with lifetime ~4 ns.     

The design, synthesis of amide KARI inhibitors and their biological activities

Ketol-acid reductoisomerase(KARI) is a promising target for the design of herbicides yet there are only few reports on the molecular design of KARI inhibitors. In this paper, based on the reported 0.165 nm high resolution crystal structure of the spinach KARI complex, 279 molecules with low binding energy toward KARI were obtained from an MDL/ACD 3D database search using the program DOCK 4.0. According to the structural information of 279 molecules provided, some amide compounds have been designed and synthesized. The bioassay results show that most of these amides had inhibitory activity to rice KARI at a test concentration of 200 μg/mL. Among which eight amides, compounds 1 and 6 show 57.4% and 48.1% inhibitory activity to KARI. The herbicidal activities of these amides were further investigated on di-cotyledonous rape (Brassica campestris) and mono-cotyledonous barnyardgrass (Echinochloa crusgalli). Compounds 1 and 6 were more favorable than others and showed 52.0% and 72.6% inhibitory activity on rape root at 100 μg/mL concentration, respectively. These amides could be further optimized for finding more potent candidates. __________ Translated from Chemical Journal of Chinese Universitiers, 2008, 29(3) (in Chinese)     

Coordination polymers of glutaraldehyde with glycine metal complexes: synthesis,spectral characterization,and their biological evaluation

Glycine metal complexes were prepared by the reaction of glycine with Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) in 1?:?2 molar ratio. Thereafter their condensation polymerization was done with glutaraldehyde to obtain polymer metal complexes. All the synthesized polymer metal complexes were characterized by elemental analysis, FT-IR, ¹H-NMR, and UV-Vis spectrometry, magnetic susceptibility, and thermogravimetric studies. The analytical data of all the polymers agreed with 1?:?1 molar ratio of metal complex to glutaraldehyde and magnetic moment data suggest that PGG–Mn(II), PGG–Co(II), PGG–Ni(II), and PGG–Cu(II) have an octahedral geometry around the metal atom, whereas the tetrahedral geometry was proposed for PGG–Zn(II) polymer. The PGG–Mn(II) and PGG–Cu(II) showed octahedral geometry. Thermal behavior of the polymer metal complexes was obtained at a heating rate of 10°C?min^?1 under nitrogen atmosphere from 0°C to 800°C. The antimicrobial activities of synthesized polymers were investigated against Streptococcus aureus, Escherichia coli, Bacillus sphaericus, Salmonella sp. (Bacteria), Fusarium oryzae, Candida albicans, and Aspergillus niger (Yeast).     

Novel 8-arylidenetetrahydroquinazoline N-oxides: synthesis,photophysical properties and biological evaluation

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Novel 2-formylpyridine 4-allyl-S-methylisothiosemicarbazone and Zn(II), Cu(II), Ni(II) and Co(III) complexes: Synthesis,characterization, crystal structure,antioxidant, antimicrobial and antiproliferative activity

New zinc (II), copper (II), nickel (II) and cobalt (III) complexes, [Zn (HL)₂]I₂ (1) , [Cu (HL)Cl₂] (2) , [Cu (HL)Br₂] (3) , [Cu (HL)(H₂O)₂](ClO₄)₂ (4) , [Ni (HL)₂]I₂·H₂O (5) , [Co(L)₂]Cl (6) , [Co(L)₂]NO₃ (7) , [Co(L)₂]I·[Co(L)₂](I₃) (8) were obtained with 2-formylpyridine 4-allyl-S-methylisothiosemicarbazone ( HL ). The isothiosemicarbazone ligand was characterized by NMR (¹H and ¹³C), IR spectroscopy and X-ray diffraction. All the complexes were characterized by elemental analysis, IR, UV–Vis, ESI-MS spectroscopy, molar conductivity, magnetic susceptibility measurements. X-ray diffraction analysis on the monocrystal and powder elucidated the structure of the complexes 1 , 5 , 7 and 8 . The ligand and the complexes were tested for their antioxidant and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Candida albicans. Also, the antiproliferative properties of these compounds on human leukemia HL-60, human cervical epithelial HeLa, human epithelial pancreatic adenocarcinoma BxPC-3, human muscle rhabdomyosarcoma spindle, large multinucleated RD cells and normal MDCK cells have been investigated. The nickel complex 5 and cobalt complexes 6 , 7 showed promising antiproliferative activity and low toxicity.     

冰片及其酯/酰胺类衍生物的合成和活性研究进展

冰片是重要的芳香开窍类中药,具有开窍醒神,清热止痛等功效,常被作为佐药与其他中药配伍使用。目前,冰片及其衍生物广泛用于医药、农药、化工及香料领域,市场前景好,研究和开发价值高。本文对天然冰片、合成冰片及其酯/酰胺类衍生物的主要合成方法和生物活性方面进行了系统总结,并对冰片酯类衍生物未来的研究方向进行了展望,以期为冰片及其酯/酰胺类衍生物的进一步的研究提供有益参考。     

Click synthesis of new 7-chloroquinoline derivatives by using ultrasound irradiation and evaluation of their biological activity

This study describes the click synthesis of new 7-chloroquinoline derivatives by using ultrasound irradiation and evaluation of their activity as antimicrobial, antimalarial and the anticancer. All the compounds show moderate antimalarial activity with IC₅₀?<?100?μM, six of them showed high antimalarial activity (2, 3, 4, 6, 8 and 9) with IC₅₀?<?50?μM. The most active 7-chloroquinoline derivative is a compound (9). Also, the newly synthesized compounds were screened for their antitumor activity towards three lines of cancer cells, MCF-7 (human breast cancer), HCT-116 (colon carcinoma) and Hela (Cervical carcinoma) cell lines. Compounds (3) and (9) exerted the highest activity on all cell lines and showed special selectivity toward MCF-7 cells and the antibacterial screening data showed moderate to good inhibition zone (12.5?±?0.63–23.8?±?1.5) towards all the tested compounds. Elucidation of the structures of these new pure compounds was based on, IR, ¹H NMR, ¹³C NMR, MS and their elemental analysis.     

The first oxalamide‐bridged ferrocene: Facile synthesis,preliminary conformational analysis and biological evaluation

tert ‐Butyl‐1′‐methoxycarbonyl‐1‐ferrocenecarbamate ( 1 ) was Boc‐deprotected to give free amine which underwent oxalyl chloride‐mediated dimerization. The structure of the so‐obtained oxalamide‐bridged ferrocene 2 was elucidated using infrared and NMR (¹H, ¹³C, COSY, NOESY, HSQC, HMBC) spectroscopies, crystal structure analysis, and electrospray ionization and high‐resolution mass spectrometry. The preliminary conformational analysis in solution suggested the intramolecular engagement of oxalamide protons, while single‐crystal analysis revealed an intermolecular hydrogen‐bonding pattern. Also, the effect of oxalamide‐bridged ferrocene 2 on cell viability of three human cell lines (HEK293T, HeLa and HepG2) was tested. In vitro screening revealed proliferative as well as cytotoxic effects of the tested compound in the applied concentration range (1–350 μM) on HEK293T and HepG2 cells. Stimulatory effect on cell growth was the most pronounced for normal HEK293T cells, while the highest cytotoxic effect was observed towards HeLa tumour cells and it was dose‐dependent. The observed dual biological activity of 2 implies its potential application in drug development.     

Design,synthesis and biological evaluation of novel 3-phenylpropanamide derivatives with acyl hydrazone units

In this study, a series of 3-phenylpropanamide derivatives with acyl hydrazone units were synthesized and characterized by ¹H NMR, ¹³C NMR and HR MS. And the structure of compound III₃₃ was confirmed by X-ray single crystal. The bioassay results showed that, compounds III₈, III₁₇, III₂₂, and III₃₄ showed excellent inhibition on Xanthomonas oryzae pv. pryzae (Xoo) with EC₅₀ values of 7.1, 8.8, 9.5, and 4.7 μg/mL in vitro. The EC₅₀ values of compounds III₁₂, III₁₄ and III₃₃ against Ralstonia solanacearum (Rs) were 7.6, 7.6 and 7.9 μg/mL, respectively, all lower than the values of thiadiazol copper (TC) was 66.8 μg/mL and bismerthiazol (BT) was 72.4 μg/mL. Compounds III₁₂, III₁₄, III₃₃, and III₃₄ exhibited excellent antibacterial activity of more than 80% against Xanthomonas axonopodis pv. citri (Xac) in vitro. Besides, compounds III₈ (51.4%) and III₃₄ (52.1%) were highly effective against Xoo in vivo, outperforming TC (49.5%) and BT (47.8%). Compounds III₈ (29.8%) and III₃₄ (24.6%) were close to TC (41.7%) and BT (47.8%) in terms of protective efficacy against Xoo in vivo. Meanwhile, some of title compounds also displayed inhibitory effects against phytopathogenic fungi. In a word, this study illustrated that the structures combined with phenylpropane amide derivatives of the acyl hydrazone units could be used as potential antibacterial reagents in the future.     

Palladium(II) complexes of 5-substituted isatin thiosemicarbazones: Synthesis,spectroscopic characterization,biological evaluation and in silico docking studies

Substituted heterocyclic (isatin) appended thiosemicarbazone ligands (L1–L3) are synthesized by condensation of substituted isatin molecule with N(4)-phenyl-3-thiosemicarbazide in good yields. The palladium(II) complexes are synthesized from ligands (L1–L3) and PdCl₂, with a general formula [PdCl(X-C₁₅H₁₀N₄OS)] where X?=?5-chloro (1), 5-bromo (2), and 5-nitro (3). Both analytical and spectroscopic methods have been used for the analysis and characterization of the synthesized compounds. The antimicrobial activity results observed that complexes, 1 and 2 have registered potent antibacterial activity against B. subtilis and K. pneumoniae and also complex 2 has shown good antifungal activity against the micro organisms. The antioxidant activity analysis revealed that the complex 3 showed significant activity with IC₅₀ values 7.24?±?0.09?µM. Moreover, the in vitro antiproliferative activity results suggested that complex 3 exhibited high activity against HeLa cell line compared with the standard with the IC₅₀ value 16.52?±?1.08?µM. The docking results correlate well.     

Design and synthesis of caged ceramide: UV-responsive ceramide releasing system based on UV-induced amide bond cleavage followed by O-N acyl transfer

Sphingolipids, recognized as membrane constructs and as key signaling molecules, have been studied to examine intracellular function. Some caged sphingolipids that release parent sphingolipids after exposure to UV-irradiation have been previously developed, but caged ceramide has yet to be reported. In this study, we report the design and synthesis of a caged ceramide. Photo-irradiation experiment clarified that the caged ceramide can be successfully converted to the parent ceramide by UV-irradiation. Introduction of an alkyne-handle moiety for further modification of the caged ceramide is also reported.     

Design and synthesis of some novel pyridothienopyrimidine derivatives and their biological evaluation as antimicrobial and anticancer agents targeting EGFR enzyme

A new series of pyridothienopyrimidine derivatives was designed and evaluated as antimicrobial and anticancer agents. The target compounds were synthesized starting with 3-aminothieno[2,3-b]pyridine-2-carboxamide derivative 1 which underwent cyclocondensation reaction with aromatic aldehydes to give the key intermediates 2a,b. By further treatment of 2a,b with various reagents, the target 2,4-disubstituted-pyrido[3′,2′:4,5]thieno[2,3-d]pyrimidines 3a,b–11a,b were obtained. To evaluate the antimicrobial activity of the new compounds, they were tested against five bacterial and five fungal strains. Compounds 6c, 8b, 9a and 9b revealed the most significant antimicrobial activity against the tested microorganisms with MIC values range (4–16 μg/mL). Also, compounds 2a,b–11a,b were screened for their in vitro cytotoxic activity against HepG-2 and MCF-7 cancer cell lines compared with doxorubicin and cisplatin as references drugs. Moreover, compounds (2b, 4a, 6a, 7b, 7c and 9a) which exhibited the most potent anticancer activity, were further subjected to EGFR^WT enzyme inhibition assay utilizing erlotinib as a standard drug. The compounds 6a, 7b, 7c and 9a which showed the most promising suppression effects were also evaluated as inhibitors against the mutant forms EGFR^L858R and EGFR^T790M. The 4-aminopyrazolone analogue 9a showed superior anticancer activity against both HepG-2 and MCF-7 cell lines (IC50 = 1.27, 10.80 μM, respectively) and more potent enzymatic inhibition activity against EGFR^WT and its mutant forms EGFR^L858R and EGFR^T790M than that obtained by erlotinib (IC₅₀ = 0.021, 0.053, 0.081 µM, respectively, IC_50erlotinib; 0.027, 0.069, 0.550 µM, respectively). Finally, the molecular docking study showed good binding patterns of the most active compounds with the prospective target EGFR^WT.     

Spectral characterization and biological evaluation of Schiff bases and their mixed ligand metal complexes derived from 4,6-diacetylresorcinol

In the present study two new series of Copper(II), Nickel(II) and Cobalt(II) complexes with two newly synthesized Schiff base ligands 4,6-bis(1-(4-bromophenylimino)ethyl)benzene-1,3-diol (H₂L¹), 4,6-bis(1-(4-methoxyphenylimino) ethyl)benzene-1,3-diol (H₂L²) and organic ligands 8-hydroxy quinoline, 1,10-phenanthroline have been prepared. The Schiff bases H₂L¹ and H₂L² ligands were synthesized by the condensation of 4,6-diacetyl resorcinol with 4-bromo aniline and 4-methoxy aniline. The ligands and their metal complexes have been characterized by FT-IR, Mass, ¹H NMR, UV–Vis., elemental analysis, ESR and Thermal gravimetric analysis. The Schiff base and their metal complexes were tested for antimicrobial activity against gram positive bacteria Staphylococcus aureus, Streptococcus pyogenes and gram negative bacteria Escherichia coli, Pseudomonas aeruginosa and fungus Candida albicans, Aspergillus niger and Aspergillus clavatus using Broth Dilution Method.     

Novel dimeric amide alkaloids from Piper chaba Hunter: isolation, cytotoxic activity, and their biomimetic synthesis

Chromatographic fractionation of methanol extract from roots of the Piper chaba Hunter resulted in the isolation of four new dimeric alkaloids, chabamide H (1), I (2), J (3), K (4) together with 11 known compounds (5-15). Their chemical structures and relative stereochemistry were determined on the basis of the comprehensive spectroscopic techniques (IR, Mass, and NMR) and further confirmed by comparison of the data with those reported in literature. In addition, cytotoxic activities of all the dimeric amides (1-7) along with their monomers (8-10) were evaluated against cervical (HELA), breast (MCF-7), liver (HEPG2), colon (HT-29), and colon (COLO-205) cancer cell lines. Among the tested isolates, 5 and 7 exhibited potent cytotoxic activity against COLO-205 cell line with IC₅₀ value of 3.10 μg/mL and 0.018 μg/mL, respectively. To prove biogenesis of the newly isolated compounds, biomimetic synthesis has also been carried out via Diels-Alder reaction by using copper(II) salts in aqueous medium.     

Novel highly fluorinated sulfamates: synthesis and evaluation of their surfactant properties

Two synthetic pathways have been elaborated to prepare new series of highly fluorinated sulfamates with excellent yields. Surface tension measurements at the air/water interface showed that these compounds constitute new excellent non-ionic surfactants exhibiting high surface activity in the range of the best non-ionic fluoro surfactants already described in the literature. The most important feature of this work is that, in comparison with the classical non-ionic fluoro surfactants, these sulfamates are easily synthesized in a monodisperse form from classical and relatively non-toxic starting materials. The critical micelle concentration (CMC), the maximum surface excess concentration (Γ) and the minimum area per molecule (a) have been calculated from the surface tension measurements on surfactant aqueous solutions. Relationships have been established between the length of both the fluorinated tail and hydrocarbon spacer linking the hydrophobic tail to the hydrophilic head, and the interfacial properties.     

Polydentate Schiff-base ligands and their Cd(II) and Cu(II) metal complexes: synthesis,characterization, biological activity and electrochemical properties

Synthesis, characterization, microbiological activity and electrochemical properties of the Schiff-base ligands A¹–A⁵ and their Cd(II) and Cu(II) metal complexes are reported. The ligands and their complexes have been characterized by elemental analysis, FT–IR, UV–Vis, ¹H- and ¹³C-NMR, mass spectra, magnetic susceptibility and conductance measurements. In the complexes, all the ligands are bidentate, the oxygen in the ortho position and azomethine nitrogen atoms of the ligands coordinate to the metal ions. The keto-enol tautomeric forms of the Schiff-base ligands A¹–A⁵ have been investigated in polar and non-polar organic solvents. Antimicrobial activity of the ligands and metal complexes were tested using the disc diffusion method and the chosen strains include Bacillus megaterium and Candida tropicalis. The electrochemical properties of the ligands A¹–A⁵ and their Cu(II) metal complexes have been investigated at different scan rates (100–500?mV?s^?1) in DMSO.     

N-(6-Methyl-2-pyridyl)acrylamide: a case of amide hydrolysis without the assistance of acid or base in the synthesis of water-driven H-bonded polymeric chains

Amide hydrolysis of N-(6-methyl-2-pyridyl)acrylamide without the assistance of either acid or base produces the aminopyridinium carboxylate salt at low or room temperature. The carboxylate ion and the free amine functionalities are cooperatively involved in hydrogen bonding with lattice water to form a new hydrogen-bonded polymeric chain.     

Novel 5H-[1,2,4]oxadiazolo[4,5-a]pyrimidin-5-one derivatives as antibacterial and anticancer agents: Synthesis and biological evaluation

A novel class of 5H-[1,2,4]oxadiazolo[4,5-a]pyrimidine derivatives was prepared, characterized, and tested for its antibacterial and anticancer potential against thirteen strains and five human cancer cell lines. The synthetic method was optimized, and a proposed reaction mechanism was also presented. The compounds containing the 5-bromo-pyrimidine moiety exhibited moderate antibacterial potencies against Gram-positive strains. Furthermore, the newly prepared compounds displayed selectively antiproliferative activity against human cancer cell lines. These current results will help us to further optimize and develop new drug candidates for clinical studies as novel antibacterial or anticancer agents.