N-Phthaloylglycinate ternary complexes with cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) metal ions and aromatic mono,bi and tridentate amines

Complexes of N-phthaloylglycinate (N-phthgly) and Co^II, Ni^II, Cu^II, Zn^II and Cd^II containing imidazole (imi), N-methylimidazole (mimi), 2,2-bipyridyl (bipy) and 1,10-phenanthroline (phen), and tridentate amines such as 2,2,2-terpyridine (terpy) and 2,4,6-(2-pyridyl)s-triazine (tptz), were prepared and characterized by conventional methods, i.r. spectra and by thermogravimetric analysis. For imi and mimi ternary complexes, the general formula [M(imi/mimi)₂(N-phthgly)₂]·nH₂O, where M = Co^II, Ni^II, Cu^II and Zn^II applies. For Cd^II ternary complexes with imi, [Cd(imi)₃(N-phthgly)₂]·2H₂O applies. For the bi and tridentate ligands, ternary complexes of the formula [M(L)(N-phthgly)₂]·nH₂O were obtained, where M = Co^II, Ni^II, Cu^II and Zn^II; L = bipy, phen, tptz and terpy. In all complexes, N-phthgly acts as a monodentate ligand, coordinating metal ions through the carboxylate oxygen, except for the ternary complexes of Co^II, Ni^II and Cu^II with mimi and Cu^II and Zn^II with imi, where the N-phthgly acts as a bidentate ligand, coordinating the metal ions through both carboxylate oxygen atoms.     

Enhancing the Anticancer Potential of Targeting Tumor-Associated Metalloenzymes via VEGFR Inhibition by New Triazolo[4,3-a]pyrimidinone Acyclo C-Nucleosides Multitarget Agents

The role of metalloenzymes in tumor progression had broadened their application in cancer therapy. Of these, MMPs and CAs are validated druggable targets that share some pivotal signaling pathways. The majority of MMPs or CAs inhibitors are designed as single-target agents. Despite their transient efficacy, these agents are often susceptible to resistance. This set the stage to introduce dual inhibitors of correlated MMPs and CAs. The next step is expected to target the common vital signaling nodes as well. In this regard, VEGFR-2 is central to various tumorigenesis events involving both families, especially MMP-2 and CA II. Herein, we report simultaneous inhibition of MMP-2, CA II, and VEGFR-2 via rationally designed hybrid 1,2,4-triazolo[4,3-a]pyrimidinone acyclo C-nucleosides. The promising derivatives were nanomolar inhibitors of VEGFR-2 (8; IC₅₀ = 5.89 nM, 9; IC₅₀ = 10.52 nM) and MMP-2 (8; IC₅₀ = 17.44 nM, 9; IC₅₀ = 30.93 nM) and submicromolar inhibitors of CA II (8; IC₅₀ = 0.21 µM, 9; IC₅₀ = 0.36 µM). Docking studies predicted their binding modes into the enzyme active sites and the structural determinants of activity regarding substitution and regioselectivity. MTT assay demonstrated that both compounds were 12 folds safer than doxorubicin with superior anticancer activities against three human cancers recording single-digit nanomolar IC₅₀, thus echoing their enzymatic activities. Up to our knowledge, this study introduces the first in class triazolopyrimidinone acyclo C-nucleosides VEGFR-2/MMP-2/CA II inhibitors that deserve further investigation.     

Coordination compounds of hydrazine derivatives with transition metals. Part 22. Reaction of aroylhydrazones with copper(II) salts

Summary Two different crystalline forms namely the greenanti and the brownsyn were isolated from the reaction of copper(II) acetate with some aldehydic aroylhydrazones, while others gave only the brown form. With copper(II) chloride, however, reduction of copper(II) ions occurred and copper(I) chelates of general formula Cu(HL)Cl were obtained. Tridentate ligands such as salicylaldehyde and pyridine-2-carbaldehyde aroylhydrazones gave copper(II) chelates Cu(L)Cl₂. A tentative reduction mechanism involving intramolecular electron transfer was proposed. In such a mechanism the steric requirements of the aroylhydrazone molecule and the presence of a third coordination site would stabilize the dipositive oxidation state of copper.     

Synthesis of 3-(L-Threo-Glycerol-l-YL)-6,7-Dimethyl-Pyrazolo[3,4-b]Quinoxalines

Abstract

Reaction of dehydro-L-ascorbic acid with 1,2-diamino-4,5-dimethylbenzene and arylhydrazines afforded 3-[l-(aryl)hydrazono-L-threo-2,3,4-trihydroxybutyl]-6,7-dimethyl-lH-quinoxalin-2-ones. Their dehydrative cyclization gave 1-aryl-3-(L-threo-glycerol-1-yl)-6,7-dimethylpyrazolo[3,4-b] quinoxalines, whose acetylation and periodate oxidation were studied.     

Silica‐supported perchloric acid as a recyclable catalyst for efficient trimethylsilyl cyanide addition to aldehydes

HClO₄? SiO₂ (0.6 mol%) acts as a highly effective catalyst for cyanation of various aldehydes to the corresponding O‐trimethylsilyl cyanohydrins, in high yields and short reaction times. Copyright © 2007 John Wiley & Sons, Ltd.     

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti‐Inflammatory Agents

The synthesis of a novel and attractive class of nonsteroidal anti‐inflammatory and antimicrobial organoiron dendrimers attached to the well‐known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram‐positive and Gram‐negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin‐resistant Staphylococcus aureus, vancomycin‐resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti‐inflammatory activities of these dendrimers are evaluated. The results of in vivo anti‐inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti‐inflammatory activity; however, second‐generation dendrimer ( G2‐D6 ) shows the best anti‐inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2‐D6  is the safest drug on biological tissues.     

Synthesis,Mesomorphic and Computational Characterizations of Nematogenic Schiff Base Derivatives in Pure and Mixed State

Homolog series based on three aromatic rings bearing terminal alkoxy chain of various lengths named 4-(4-(alkoxy)phenylimino)methyl)phenyl nicotinate (An) were synthesized. The alkoxy-chain length changed between 6, 8 and 16 carbons. Mesomorphic and optical properties were carried out via differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Elemental analyses, FT-IR and NMR spectroscopy were carried out to elucidate the molecular structures of the prepared derivatives. Mesomorphic results indicated that all the synthesized homologs (An) are monomorphic possessing the nematic (N) phase enantiotropically with wide thermal stability. Computational simulations were measured via density functional theory (DFT) theoretical calculation tool. The estimated thermal and geometrical parameters are in agreement with the experimental data. By discussing the estimated parameters, it was found that the molecular architecture, dipole moment and the polarizability of the investigated compounds are highly affected by the length of the attached terminal flexible chain and the location of the nitrogen atom in the other terminal aromatic ring. Binary phase diagrams of two corresponding homologs with different proportionating terminals were constructed, and their binary phase physical properties were discussed in terms of the temperature range and stability of the N phase.     

Simple chromatographic detection modes for antitumor agent and its degradants

Degradation of active ingredients is common during the production, transportation, and storage of the pharmaceutical preparations. The resulted degradation products can affect the pharmaceuticals’ therapeutic effect. Also, they may have some toxic properties that make them have deleterious effects on patients. Nifuroxazide, antitumor, antimetastasis, and antidiarrheal agent, has been detected in pharmaceutical formulation by two sensitive, selective, and cheap methods. The first method was densitometric thin-layer chromatography technique. The compound was detected in the presence of its degradation products without any interference. Limits of quantification and detection values were 200 and 94.3?ng/band, respectively. The method was linear in the range 0.2–12?µg/band with mean recovery% ±relative standard deviation (RSD)%?=?99.97%?±?1.414. The second method was developed using simple high-performance liquid chromatography technique. The method was successfully able to separate the proposed compound from its degradation forms in the presence of pentoxiftylline as an internal standard without any interference in less than 5?min. The method also detected nifuroxazide degradation products down to 500?ng/mL. Both methods were statistically compared to a reported method with no significant difference in performance.