Mercury(II) and thallium(III) organometallic derivatives of 2-Mercaptobenzoxazole

Some derivatives of 2-mercaptobenzoxazole (HL) of the type MRnL [M = Hg or Tl, R = Me or Ph and n = 1 (Hg) or 2 (Tl)] have been prepared. The structure of HgMeL has been determined by an X-ray diffraction study; in the crystal there are two independent planar molecules in each asymmetric unit, with the ligand in its thiolic form and an almost linear CHgS linkage. Weak intramolecular and intermolecular secondary interactions complement the mercurysulphur bond. The spectroscopic (IR, Raman, mass, 13C-NMR), conductimetric, and dipolar properties of this and the other compounds are discussed. © 1991.

Theoretical insight into the mechanism for the inhibition of the cysteine protease cathepsin B by 1,2,4-thiadiazole derivatives

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Synthesis and antitubercular evaluation of new 1,2,3-triazole derivatives of carbohydrates

Coordenação de Pessoal de Nível Superior (CAPES)

Caco-2 cells cytotoxicity of nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA)

It is important to determine the toxicity of compounds and co-solvents that are used in cell monolayer permeability studies to increase confidence in the results obtained from these in vitro experiments. This study was designed to evaluate the cytotoxicity of new nifuroxazide derivatives with potential activity against Methicillin-resistant Staphylococcus aureus (MRSA) in Caco-2 cells to select analogues for further in vitro permeability analyses. In this study, nitrofurantoin and nifuroxazide, in addition to 6 furanic and 6 thiophenic nifuroxazide derivatives were tested at 2, 4, 6, 8 and 10 mu g/mL. In vitro cytotoxicity assays were performed according to the MTT (methyl tetrazolium) assay protocol described in ISO 10993-5. The viability of treated Caco-2 cells was greater than 83% for all tested nitrofurantoin concentrations, while those treated with nifuroxazide at 2, 4 and 6 mu g/mL had viabilities greater than 70%. Treatment with the nifuroxazide analogues resulted in viability values greater than 70% at 2 and 4 mu g/mL with the exception of the thiophenic methyl-substituted derivative, which resulted in cell viabilities below 70% at all tested concentrations. Caco-2 cells demonstrated reasonable viability for all nifuroxazide derivatives, except the thiophenic methyl-substituted compound. The former were selected for further permeability studies using Caco-2 cells. (C) 2012 Elsevier Ltd. All rights reserved.

Synthesis, anti-inflammatory activity and molecular docking studies of 2,5-diarylfuran amino acid derivatives

A series of 2,5-diaryl substituted furans functionalized with several amino acids were synthesized and evaluated as the cyclooxygenases COX-1 and COX-2 enzymes inhibitors. The proline-substituted compound inhibited PGE(2) secretion by LPS-stimulated neutrophils, suggesting selectivity for COX-2. Molecular docking studies in the binding site of COX-2 were performed. (C) 2011 Elsevier Masson SAS. All rights reserved.

The ω3-polyunsaturated fatty acid derivatives AVX001 and AVX002 directly inhibit cytosolic phospholipase A(2) and suppress PGE(2) formation in mesangial cells

ω3-polyunsaturated fatty acids (ω3-PUFAs) are known to exert anti-inflammatory effects in various disease models although their direct targets are only poorly characterized.

Syntheses and characterization of monomeric Mo(VI) complexes with bidentate phosphine oxide ligands and dimeric and tetrameric Mo(V) clusters with benzoic acid and phosphinic acid derivatives, containing MoO2, Mo2O2(μ-O)2 and Mo4O4(μ3-O)4

Mo(VI) oxo complexes have been persistently sought after as epoxidation catalysts. Further, Mo(V) oxo clusters of the form M4(µ3-X)4 (M = transition metal, X = O, S) have been rigorously studied due to their remarkable structures and also their usefulness as models for electronic studies. The syntheses and characterizations of new Mo(VI) and Mo(V) oxo complexes have been described in this dissertation. Two new complexes MoO2Cl2Ph2P(O)CH2COOH and MoO2Cl2Ph2P(O)C6H4tBuS(O) were synthesized from reactions of “MoO2Cl2” with ligands Ph2P(O)CH2COOH and Ph2P(O)C6H4tBuS(O). Tetrameric packing arrangements comprised of hydrogen bonds were obtained for the complex MoO2Cl2Ph2P(O)CH2COOH and the ligand Ph2P(O)CH2COOH. Further the stability of an Mo-O bond was preferred over the Mo-S bond even though this resulted in the formation of a more strained seven membered ring. Tetranuclear Mo(V) complexes of the form [Mo4(µ3-O)4(µ-O2PR2)4O4], (PR2 = PPh2, PMe2) were synthesized using reactions of MoO2(acac)2 with diphenyl and dimethyl phosphinic acids, in ethanol. In the crystal structure of these complexes four Mo=O units are interconnected by four triply bridging oxygen atoms and bridging phosphinate ligands. The complex exhibited fourfold symmetry as evidenced by a single 31P NMR peak for the P atoms in the coordinated ligands. Reaction of WO2(acac)2 with Ph2POOH in methanol resulted in a dimeric W(VI) complex [(CH3O)2(O)W(µ-O)( µ-O2PPh2)2W(O)(CH3O)2] which contained a packing disorder in its crystal structure. Similar reactions of MoO2(acac)2 with benzoic acid derivatives resulted in dimeric complexes of the form [Mo2O2(acac)2(µ-O)(µ-OC2H5)(µ-O2CR)] (R = C6H5, (o-OH)C6H4, (p-Cl)C6H4, (2,4-(OH)2)C6H3, (o-I)C6H4) and one tetrameric complex [Mo2O2(acac)2(µ-O)(µ-OC2H5)(µ-O2C)C6H4(p-µ-O2C)Mo2O2(acac)2(µ-O)(µ-OC2H5)] with terephthalic acid. 1H NMR proved very useful in the prediction of the formation of dimers with the substituted benzoic acids, which were also confirmed by elemental analyses. The reductive capability of ethanol proved instrumental in the syntheses of Mo(V) tetrameric and dimeric clusters. Synthetic details, IR, 1H and 31P NMR spectroscopy and elemental analyses are reported for all new complexes. Further, single crystal X-ray structures of MoO2Cl2Ph2P(O)CH2COOH, MoO2Cl2Ph2P(O)C6H4tBuS(O), [Mo4(µ3-O)4(µ-O2PR2)4O4], (PR2 = PPh2, PMe2), [(CH3O)2(O)W(µ-O)( µ-O2PPh2)2W(O)(CH3O)2] and [Mo2O2(acac)2(µ-O)(µ-OC2H5)(µ-O2CR)] (R = C6H5, (o-OH)C6H4) are also presented.

Trifluoroacetic acid: A more effective and efficient reagent for the synthesis of 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones and 3-arylmethyl-2-amino quinolines from Baylis-Hillman derivatives via Claisen rearrangement

Trifluoroacetic acid has been discovered to be a highly effective and efficient reagent for the tandem Claisen rearrangement and cyclisation reaction to yield 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones from compounds obtained from the SN2 reaction between anilines and acetyl derivatives of Baylis-Hillman adducts of acrylates in the presence of DABCO. In contrast similar compounds obtained from the acetyl derivatives of Baylis-Hillman adduct of acrylonitrile on treatment with trifluoroacetic acid directly furnish 3-arylmethyl-2-amino-quinoline via tandem Claisen rearrangement, cylisation and isomerisation.

Simple and efficient synthesis of substituted 2-pyrrolidinones, 2-pyrrolones and pyrrolidines from enaminones of Baylis-Hillman derivatives of 3-isoxazolecarbaldehydes

The enaminones, generated from derivatives of appropriately substituted Baylis-Hillman adducts of 3-isoxazolecarbaldehydes undergo intramolecular ring-closure reactions to afford substituted 2-pyrrolidinones, 1,5-dihydro-2-pyrrolones and N-substituted pyrrolidines in good yields.

High yield conversion of doxorubicin to 2-pyrrolinodoxorubicin, an analog 500-1000 times more potent: structure-activity relationship of daunosamine-modified derivatives of doxorubicin.

A convenient, high yield conversion of doxorubicin to 3'-deamino-3'-(2''-pyrroline-1''-yl)doxorubicin is described. This daunosamine-modified analog of doxorubicin is 500-1000 times more active in vitro than doxorubicin. The conversion is effected by using a 30-fold excess of 4-iodobutyraldehyde in anhydrous dimethylformamide. The yield is higher than 85%. A homolog of this compound, 3'-deamino-3'-(1'',3''-tetrahydropyridine-1''-yl)doxorubicin, was also synthesized by using 5-iodovaleraldehyde. In this homolog, the daunosamine nitrogen is incorporated into a six- instead of a five-membered ring. This analog was 30-50 times less active than its counterpart with a five-membered ring. A similar structure-activity relationship was found when 3'-deamino-3'-(3''-pyrrolidone-1''-yl)doxorubicin (containing a five-membered ring) and 3'-deamino-3'-(3''-piperidone-1''-yl)doxorubicin (with a six-membered ring) were tested in vitro, the former being 5 times more potent than the latter. To further elucidate structure-activity relationships, 3'-deamino-3'-(pyrrolidine-1''-yl)doxorubicin, 3'-deamino-3'-(isoindoline-2''-yl)doxorubicin, 3'-deamino-3'-(2''-methyl-2''-pyrroline-1''-yl)doxorubicin, and 3'-deamino-3'-(3''-pyrroline-1''-yl)doxorubicin were also synthesized and tested. All the analogs were prepared by using reactive halogen compounds for incorporating the daunosamine nitrogen of doxorubicin into a five- or six-membered ring. These highly active antineoplastic agents can be used for incorporation into targeted cytotoxic analogs of luteinizing hormone-releasing hormone intended for cancer therapy.

Derivatives of 3,3-dimethyl 2-cyan 2-carboxethyl cyclopentanone /

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Synthesis and characterization of Pd(II) and Pt(II) complexes with triazolopyrimidine derivatives: The crystal structure of [Pd2L2Cl4] where L=5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine

The Pd(II) and Pt(II) complexes with triazolopyrimidine C-nucleosides L-1 (5,7-dimethyl-3-(2',3',5'-tri-O-benzoyl-beta-D-ribofuranosyl-s-triazolo)[4,3-a]pyrimidine), L-2 (5,7-dimethyl-3-beta-D-ribofuranosyl-s-triazolo [4,3-a]pyrimidine) and L-3 (5,7-dimethyl[1,5-a]-s-triazolopyrimidine), [Pd(en)(L-1)](NO3)(2), (Pd(bpy)(L-1)](NO3)(2), cis-Pd(L-3)(2)Cl-2, [Pd-2(L-3)(2)Cl-4]center dot H2O, cis-Pd(L-2)(2)Cl-2 and [Pt-3(L-1)(2)Cl-6] were synthesized and characterized by elemental analysis and NMR spectroscopy. The structure of the [Pd-2(L-3)(2)Cl-4]center dot H2O complex was established by Xray crystallography. The two L-3 ligands are found in a head to tail orientation, with a (PdPd)-Pd-... distance of 3.1254(17) angstrom.L-1 coordinates to Pd(II) through N8 and N1 forming polymeric structures. L-2 coordinates to Pd(II) through N8 in acidic solutions (0.1 M HCl) forming complexes of cis-geometry. The Pd(II) coordination to L-2 does not affect the sugar conformation probably due to the high stability of the C-C glycoside bond. (c) 2006 Elsevier B.V. All rights reserved.