Fourteen new fosmidomycin analogues with altered metal chelating groups were prepared and evaluated for inhibition of E. coli Dxr, M. tuberculosis Dxr and the growth of P. falciparum K1 in human erythrocytes. None of the synthesized compounds showed activity against either enzyme or the Plasmodia. This study further underlines the importance of the hydroxamate functionality and illustrates that...

Pasteurella multocida grown under conditions of iron deprivation secreted into the culture medium a growth-enhancing factor which functioned as a siderophore. The siderophore was found to be neither a phenolate nor a hydroxamate by chemical tests and bioassays and was given the trivial name multocidin. Multocidin was partially purified and found to be a highly polar, nonaromatic, and dialyzable...

The preparation of cyclic hexapeptides from N-hydroxy tripeptides building blocks is described. Introduction of an unsaturated chain on the hydroxamate oxygen followed by fragment coupling leads to N,N'-dialkenoxy hexapeptides that are efficiently cyclized through a ring-closing metathesis reaction. The length of the alkene chains allows the modulation of the ring size: the synthesis of 17- and...

Pseudomonas aeruginosa (GRC1) isolated from potato rhizosphere, grew better on succinate medium than tryptic soy medium and produced hydroxamate type of siderophore in iron-deficient succinate medium. When the strain GRC1 was grown in the presence of different metal ion compounds, viz. ZnSO4, MnSO4, MnCl2 and FeCl3 at 6 and 12 microM concentrations individually, ZnSO4 (12 microM) promoted sider...

The strategic recombination of preformed coordination clusters in the presence of polymodal bridging ligands has successfully led to the characterisation of five new compounds of structural and magnetic interest. Indeed using the dinuclear complex [M2(H2O)(piv)4(Hpiv)4] (M = Co, Ni; Hpiv = pivalic acid) as starting material and reacting it with phenylhydroxamic acid (H2pha) has yielded the four...

The in situ formation and subsequent Cu(ii) ligation of the polydentate pro-ligands o-[(E)-(2-hydroxy-3-methoxyphenyl)methylideneamino]benzohydroxamic acid (L1H3), o-[(E)-(2-hydroxy-3-methoxy-5-bromophenyl)methylideneamino]benzohydroxamic acid (L2H3) and o-[(E)-(2-hydroxyphenyl)methylideneamino]benzohydroxamic acid (L3H3), leads to the self-assembly of the cages [Cu(ii)10(L1)4(2-aph)2(H2O)2](Cl...

Overexpression of matrix metalloproteinases (MMPs) facilitates tumor cell invasion. Synthetic MMP inhibitors such as batimastat have been designed to treat cancer. We report that because of batimastat treatment, human breast carcinoma cells metastasized to the liver in nude mice and that an increase of liver metastases of murine T-cell lymphoma cells was observed in syngeneic mice. Batimastat t...

Ferrioxamines-mediated iron acquisition by Streptomyces coelicolor A3(2) has recently received increased attention. In addition to the biological role of desferrioxamines (dFOs) as hydroxamate siderophores, and the pharmaceutical application of dFO-B as an iron-chelator, the ferrioxamines have been shown to mediate microbial interactions. In S. coelicolor the siderophore-binding receptors DesE ...

For the fungus Histoplasma capsulatum, and for other microbial pathogens, iron is an essential nutrient. Iron sequestration in response to infection is a demonstrated host defense mechanism; thus, iron acquisition may be considered an important pathogenic determinant. H. capsulatum is known to secrete Fe(III)-binding hydroxamate siderophores, which is one common microbial process for acquiring ...

Human enhancer of zeste 2 (EZH2) protein belongs to the multiprotein polycomb repressive complex 2, which also includes suppressor of zeste 12 (SUZ12) and embryonic ectoderm development (EED). The polycomb repressive complex 2 complex possesses histone methyltransferase activity mediated by the Su(var)3-9, enhancer of zeste, and trithorax domain of EZH2, which methylates histone H3 on lysine (K...