Facile Synthesis of N (alpha) -Protected Amino/Peptide Hydroxamic Acids Mediated by COMU

One-pot preparation of N (alpha) -protected amino/peptide hydroxamic acids from corresponding carboxylic acids is described using uronium-type coupling reagent COMU. The present protocol is simple and mild conditions are used. Thus the resulting hydroxamic acids are obtained in good yields without racemization

[(?6 -p-cymene)Ru(H2O)3] 2+ Binding Capability of Aminohydroxamates - A Solution and Solid State Study

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Facile Synthesis of N α -Protected Amino/Peptide Hydroxamic Acids Mediated by Comu

One-pot preparation of N α -protected amino/peptide hydroxamic acids from corresponding carboxylic acids is described using uronium-type coupling reagent COMU. The present protocol is simple and mild conditions are used. Thus the resulting hydroxamic acids are obtained in good yields without racemization

Interaction of Imidazole Containing Hydroxamic Acids with Fe(III): Hydroxamate Versus Imidazole Coordination of the Ligands

Solution equilibrium studies on Fe(III) complexes formed with imidazole-4-carbohydroxamic acid (Im-4-Cha), N-Me-imidazole-4-carbohydroxamic acid (N-Me-Im-4-Cha), imidazole-4-acetohydroxamic acid (Im-4-Aha), and histidinehydroxamic acid (Hisha) have been performed by using pH-potentiometry, UV-visible spectrophotometry, EPR, ESI-MS, and H1-NMR methods. All of the obtained results demonstrate that the imidazole moiety is able to play an important role very often in the interaction with Fe(III), even if this metal ion prefers the hydroxamate chelates very much. If the imidazole moiety is in α-position to the hydroxamic one (Im-4-Cha and N-Me-Im-4-Cha) its coordination to the metal ion is indicated unambiguously by our results. Interestingly, parallel formation of (Nimidazole, Ohydroxamate), and (Ohydroxamate, Ohydroxamate) type chelates seems probable with N-Me-Im-4-Cha. The imidazole is in β-position to the hydroxamic moiety in Im-4-Aha and an intermolecular noncovalent (mainly H-bonding) interaction seems to organize the intermediate-protonated molecules in this system. Following the formation of mono- and bishydroxamato mononuclear complexes, only EPR silent species exists in the Fe(III)-Hisha system above pH 4, what suggests the rather significant “assembler activity” of the imidazole (perhaps together with the ammonium moiety)

Hydroxamate-complexes of half-sandwich platinum metal ions: solution equilibrium studies and synthesis

A dolgozatban a potenciálisan rákellenes hatású, félszendvics szerkezetű platinafémionok hidroxámsavakkal való kölcsönhatását vizsgáltuk. Oldategyensúlyi módszerekkel vizsgáltuk a képződő fémkomplexek összetételét és stabilitását, valamint szilárd formában is előállítottuk, és szerkezetileg is jellemeztük azokat. Az előállított vegyületek rákos sejteken való biológiai tesztjét is elvégeztük.In this work we have studied the interaction of the potential anticancer agent half-sandwich platinum metal ions, with hydroxamic acids. We have examined the complex formation with solution equilibrium methods, and we have prepared and characterized the metal complexes formed also in the solid state. The in vitro cytotoxicity of the prepared complexes was also tested on selected cancer cell lines

Metallacrowns of Ni(II) with alpha-aminohydroxamic acids in aqueous solution: beyond a 12-MC-4, an unexpected (vacant?) 15-MC-5

Growing attention has been devoted in the recent years to a class of metallamacrocycles known as metallacrowns (MCs). They are structural analogues of crown ethers where the methylene bridges have been substituted by coordinative bonds formed by a transition metal ion ("ring" metal) and a nitrogen atom. The cavity of the metallacrown can accommodate an additional metal ion ("core" metal) either identical or different from the ring metal, thus forming a homo- or hetero-metallic MC. The most studied ring metal ion is certainly Cu(2+) and the aminohydroxamic acids have proved to be very suitable ligands to form MCs. The behavioural analogies between Cu(2+) and Ni(2+) in forming complexes, along with recent literature data in the solid state, prompted us to investigate the possible MC formation between Ni(2+) and both (S)-α-alaninehydroxamic acid and (S)-valinehydroxamic acid, in aqueous solution. Two metallacrowns, a 12-MC-4 and an unexpected 15-MC-5 have been detected by potentiometry and confirmed by ESI-MS results. Their structures are discussed on the basis of potentiometric, calorimetric, spectroscopic data and DFT calculations. The existence of a vacant 15-MC-5 species in solution can be put forward for the first time, making the present metal/ligand systems very interesting for their potential applications in cation recognition and separation. Finally, the crystal structure of the binary complex K[NiL(2)H(-1)]·5/3 H(2)O of (S)-α-alaninehydroxamic acid (LH) is also reported

Two-pronged attack: dual inhibition of Plasmodium falciparum M1 and M17 metalloaminopeptidases by a novel series of hydroxamic acid-based inhibitors

Plasmodium parasites, the causative agents of malaria, have developed resistance to most of our current antimalarial therapies, including artemisinin combination therapies which are widely described as our last line of defense. Antimalarial agents with a novel mode of action are urgently required. Two Plasmodium falciparum aminopeptidases, PfA-M1 and PfA-M17, play crucial roles in the erythrocytic stage of infection and have been validated as potential antimalarial targets. Using compound-bound crystal structures of both enzymes, we have used a structure-guided approach to develop a novel series of inhibitors capable of potent inhibition of both PfA-M1 and PfA-M17 activity and parasite growth in culture. Herein we describe the design, synthesis, and evaluation of a series of hydroxamic acid-based inhibitors and demonstrate the compounds to be exciting new leads for the development of novel antimalarial therapeutics