Medicinal Chemistry Biochemistry Organic Synthesis Bioinorganic Chemistry

Molecular Structure and Antimicrobial Activity of a Luminescent Dinuclear Silver(I) Complex of Phenyl-bis(2-pyridyl)phosphine

by Cina Foroutan-Nejad

Ali Nemati Kharat, Abolghasem Bakhoda, Sahar Foroutannejad, Cina Foroutan-Nejad, ZAAC, 2011, 637, 2260

Phenyl bis(2-pyridyl)phosphine [PhP(2-py)2] and its silver
nitrate complex of formula [Ag2(μ-(PhP(2-py)2)2(NO3)2]... more Phenyl bis(2-pyridyl)phosphine [PhP(2-py)2] and its silver
nitrate complex of formula [Ag2(μ-(PhP(2-py)2)2(NO3)2] (1) were synthesized
and characterized by elemental analysis, IR spectroscopy, single-
crystal X-ray diffraction, and computational studies. The silver(I)
complex 1 with a 1:1 metal-ligand molar ratio is dinuclear cluster with silver atoms in same environments. Biological studies, carried out in
vitro against wide range of gram positive and gram negative bacteria,
have shown that the free [PhP(2-py)2] ligand and its silver complex
show distinct differences in the biological properties.

Design and Synthesis of Thiadiazoles and Thiazoles Targeting the Bcr-Abl T315I Mutant: from Docking False Positives to ATP-Noncompetitive Inhibitors

by Marco Radi

In an effort to optimize our previously identified dual Src/Abl hits, a new series of 1,3,4-thiadiazoles and... more In an effort to optimize our previously identified dual Src/Abl hits, a new series of 1,3,4-thiadiazoles and 1,3-thiazoles were designed and synthesized, paying particular attention to the reduction of their lipophilicity and to the improvement of the affinity towards the drug-resistant T315I mutant. Compound 5 was identified as a promising allosteric inhibitor of the T315I mutant.

Src kinase inhibitors: an update on patented compounds

by Marco Radi

The cytoplasmatic tyrosine in kinase c-Src is involved in the regulation of several cell functions including adhesion,... more The cytoplasmatic tyrosine in kinase c-Src is involved in the regulation of several cell functions including adhesion, invasion, proliferation, survival and angiogenesis. Src activity is strictly regulated in healthy cells, whereas its overexpression or hyperactivation plays a critical role during tumor development. Recently it has been suggested that the oncogenic potential of Src is linked to its role in the activation of key signaling molecules involved in several cell pathways, rather than its direct activity. For all these reasons Src represents a promising therapeutic target for the treatment of tumors. In this article a number of examples of c-Src inhibitors appeared in selected patents from 2006 to early 2011 will be reported, focusing on their chemical features and, whenever possible, on structureactivity relationships and mechanism of action. Examples of type I or II ATP-competitive inhibitors or substrate competitive inhibitors will be presented. The research in this field is very active and will probably lead to the discovery of therapeutically useful compounds, both c-Src selective and multitargeted inhibitors, that acting on different cell pathways could be more effective in blocking cancer development. However, only the results of clinical trials will show in the near future the most promising compounds.

A comparison of the binding of metal complexes to duplex and quaruplex DNA

by Kimberley Davis

Effective Repression of the Fragmentation of a Hexadentate Ligand Bearing An Auto-Immolable Pendant Arm by Iron Coordination

by Vitalie Stavila

Reinvestigation of the roles of the carbonyl group of glutathione with yeast glyoxalase I: Implications to the mechanism and co-enzymic role of glutathione.

by Claudius D'Silva

Febs. Lett., 1986, 202, 240-244.

Phoaffinity labelling of yeast glutathione reductase by a bifunctional aryl azide derivative of oxidised glutathione .

by Claudius D'Silva

Photobiochem & Photobiophys., 1983, 5, 151-158.

Photoaffinity labelling of glutaredoxin from Escheria. coli.

by Claudius D'Silva

Biochem.Biophys.Res. Commun, 1982, 138, 59-61

Glutathione derivatives as inhibitors of ribonucleotide reductase from E.coli

by Claudius D'Silva

Febs. Letts, 1982, 138, 59-61

Photoaffinity labels for glutathione and glutathione disulphide utilising systems.

by Claudius D'Silva

Trans.Biochem. Soc. 1982, 10, 124-125.

The Therapeutic Potential of Inhibitors of the trypanathione Cycle

by Claudius D'Silva

Structure-Activity Study on the in Vitro Antiprotozoal Activity of Glutathione Derivatives

by Claudius D'Silva

QSAR Study on the Contribution of Log P and Es to the in Vitro Antiprotozoal Activity of Glutathione Derivatives

by Claudius D'Silva

The activity of bacteriocins from Carnobacterium maltaromaticum UAL307 against Gram‐negative bacteria in combination with EDTA treatment

by Yoganathan Sabesan

Bacteriocins from Gram-positive bacteria are potent antimicrobial peptides that inhibit pathogenic and food-spoilage... more Bacteriocins from Gram-positive bacteria are potent antimicrobial peptides that inhibit pathogenic and food-spoilage bacteria. They are usually ineffective against Gram-negative bacteria because they cannot penetrate the outer membrane (OM). Disruption of the OM of some Gram-negative bacteria was reported to sensitize them to certain bacteriocins. This study evaluates the activity of three purified bacteriocins [carnocyclin A (CclA), carnobacteriocin BM1 (CbnBM1) and piscicolin 126 (PisA)] produced by Carnobacterium maltaromaticum UAL307, which has been approved for preservation of food in United States and Canada, against three Gram-negative bacteria (Escherichia coli DH5α, Pseudomonas aeruginosa ATCC 14207 and Salmonella Typhimurium ATCC 23564). Their efficacy is compared with bacteriocins of other classes: the lantibiotics nisin A (positive control) and gallidermin, and the cyclic peptide subtilosin A (SubA). In combination with EDTA, CclA inhibited both E. coli and Pseudomonas. PisA inhibited Pseudomonas, but CbnBM1 showed weak activity toward Pseudomonas. In comparison, nisin and gallidermin inhibited the growth of all three strains, whereas SubA was active against E. coli and Pseudomonas only at high concentrations. The results reveal that UAL307 bacteriocins can inhibit Gram-negative bacteria if the OM is weakened, and that the different classes of bacteriocins in this study exert unique modes of action toward such bacteria.

Synthesis of pseudo-C-nucleosides from beta-formyl-alpha,beta-unsaturated ester bearing a beta-furanosidic moiety

by M. Isabel Ismael

Abstract Pseudo-C-nucleosides have potential biological
activity, and an efficient synthesis of new... more Abstract Pseudo-C-nucleosides have potential biological
activity, and an efficient synthesis of new pseudo-C-nucleosides
has been developed via the reaction of a b-formyl-a,bunsaturated
ester bearing a b-sugar moiety with hydrazines in
neutral and acidic conditions. The preparation of the b-formyl-
a,b-unsaturated ester was accomplished by oxidation of
the secondary hydroxyl group of 3-O-benzyl-1,2-O-isopropylidene-
a-D-glucofuranose, followed by elongation of its
carbon chain with (ethoxycarbonylmethylene)triphenylphosphorane
and oxidation of the hydroxymethyl group.

Keywords Carbohydrates Heterocycles
Pseudo-C-nucleosides  Pyridazinone  Wittig reaction

"Synthesis of Phenylseleno Sugars From Epoxides and of alpha,beta-Unsaturated Carbonyl Derivatives For the Study of Their Insecticidal Activity"

by M. Isabel Ismael

"Synthesis of Phenylseleno Sugars From Epoxides and of alpha,beta-Unsaturated Carbonyl Derivatives For the Study of Their Insecticidal Activity",
Amélia P. Rauter, Tana Canda, Jorge Justino, Maria I. Ismael, José A. Figueiredo, J. Carbohydr. Chem., 23 (4), 239-251, 2004.

"Pseudo-C-Nucleosides bearing Heterocyclic Moieties as Acetylcholinesterase Inhibitors"

by M. Isabel Ismael

"Pseudo-C-Nucleosides bearing Heterocyclic Moieties as Acetylcholinesterase Inhibitors", M. I. Ismael, J. A. Figueiredo, J. M. Pinheiro, A. M. S. Silva, A. P. Rauter, J. Justino, M. Goulart, D. Mira, F. V. M. Silva, Revista Portuguesa de Farmácia, Volume LII (nº 3) Suplemento (ISSN 0484-811 X), 2008

Incorporation of Phosphole Moieties into the Side Chain of Tyrosine and Phenylalanine

by Fabrice Bisaro

Fabrice Bisaro*, Pascal Le Floch
Laboratoire ‘Hétéroéléments et Coordination', Ecole Polytechnique, CNRS, 91128 Palaiseau Cedex, France. Synlett 2010, No. 20, 3081–3085.
Fax: +33(0)169334440; e-Mail: fabrice.bisaro@wolfson.oxon.org;

A tyrosine derivative with a phosphole moiety covalently attached to the phenolic hydroxy group was successfully... more A tyrosine derivative with a phosphole moiety covalently attached to the phenolic hydroxy group was successfully prepared through P-O bond-forming reaction, via a nucleophilic substitution reaction at the phosphorus, by slow addition of N-CBz-protected tyrosine methyl ester to a chlorophosphole adduct in the presence of triethylamine, albeit with a low yield. Furthermore, a phenylalanine derivative with a phosphole-containing side chain was conveniently synthesized by Stille cross-coupling reaction of a stannylphosphole reagent with N-Boc-protected 4-iodophenylalanine methyl ester, using Pd(dba)2 as catalyst, in the absence of any additional ligand. These molecules must be seen as valuable building blocks for the preparation of metalloproteins of interest for chemical, biological, and medical applications.