Abstract:
:The cysteine proteases of the trypanosomatid parasitic protozoa have been validated as targets for chemotherapy of Chagas' disease and leishmaniasis. Metal complexes of gold, platinum, iridium, palladium, rhodium and osmium have been reported to have activity against a variety of trypanosomatids, but the molecular target of these compounds has not been defined. The activity of gold(III) and palladium(II) cyclometallated complexes, and oxorhenium(V) complexes against mammalian and parasitic cysteine proteases was investigated. All gold(III) complexes (1-6) inhibited cathepsin B with IC(50) values in the range of 0.2-1.4 microM. Of the six palladium compounds, aceto[2,6-bis[(butylthio-kappa S)methyl]phenyl-kappa C]-, (SP-4-3)-palladium(II) (11) was the most potent inhibitor of cathepsin B with an IC(50) of 0.4 microM. A clear structure-activity relationship was observed with the oxorhenium(V) complexes with chloro[2,2'-(thio-kappa S)bis[ethanethiolato-kappa S)]] oxorhenium(V) (16) being the most potent inhibitor of cathepsin B with an IC(50) of 0.009 microM. Six complexes were further tested against the parasite cysteine proteases, cruzain from T. cruzi, and cpB from L. major; the most potent inhibitors were the two rhenium complexes (2(1H)-pyridinethionato-kappa S(2))[2,6-bis[(mercapto-kappa S)methyl]pyridine-kappa N(1)] oxorhenium(V) (15) and chloro[2,2'-(thio-kappa S)bis[ethanethiolato-kappa S)]] oxorhenium(V) (16). The compounds were also evaluated in assays for parasite growth. Two oxorhenium(V) compounds ((p-methoxyphenylthiolato-S)[2,6-bis[(mercapto-kappa S)methyl]pyridine-kappa N(1)] oxorhenium(V) (14) and (methanethiolato)[2,2'-(thio-kappa S)bis[ethanethiolato-kappa S)]] oxorhenium (V) (18)) and the palladium compound 11 inhibited T. cruzi intracellular growth, and compound 11 inhibited promastigote growth in three Leishmania species. In conclusion this preliminary data indicates that metal complexes targeted at parasite cysteine proteases show promise for the treatment of both Chagas' disease and leishmaniasis.
journal_name
J Inorg Biochemjournal_title
Journal of inorganic biochemistryauthors
Fricker SP,Mosi RM,Cameron BR,Baird I,Zhu Y,Anastassov V,Cox J,Doyle PS,Hansell E,Lau G,Langille J,Olsen M,Qin L,Skerlj R,Wong RS,Santucci Z,McKerrow JHdoi
10.1016/j.jinorgbio.2008.05.010subject
Has Abstractpub_date
2008-10-01 00:00:00pages
1839-45issue
10eissn
0162-0134issn
1873-3344pii
S0162-0134(08)00138-4journal_volume
102pub_type
杂志文章abstract::Anhydrotetracycline (AHTC) is the major toxic decomposition product of the antibiotic tetracycline. The complexation of AHTC to Mg(II), Al(III), and Fe(III) was studied in aqueous medium using absorption and circular dichroism measurements. The study of the Mg(II)-AHTC interactions at pH 7 indicated the formation of t...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(95)00017-i
更新日期:1995-11-15 00:00:00
abstract::The N-terminal protected and unprotected peptides MAHHEEQHG-NH(2), Ac-MAHHEEQHG-NH(2) from Hpn (Helicobacter histidine-rich protein) and MAHHEQQQQQQA-NH(2), Ac-MAHHEQQQQQQA-NH(2) from Hpn-like protein, respectively, were synthesized and their interactions with Cu(2+) and Ni(2+) ions were studied by potentiometric, UV-...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2010.11.004
更新日期:2011-02-01 00:00:00
abstract::Metallodrugs have become an integral part of modern medicinal chemistry with platinum drugs as anti-cancer agents being well-known examples. The historically interesting compound Zeise's salt, potassium trichlorido(ethene)platinate(II) has scarcely been investigated in this context yet. This study is geared towards sh...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2018.09.003
更新日期:2018-12-01 00:00:00
abstract::The first reported homogenous rare earth curcumin (HCurc; ((1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione)) complexes with the formula ML3, where M(3+) is Eu(III), Gd(III) or Lu(III), were synthesized and characterized by mass spectrometry, infrared spectroscopy and, in the case of the lutetium co...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2013.12.004
更新日期:2014-03-01 00:00:00
abstract::Catalase (CAT) and myeloperoxiase (MPO) are heme-containing enzymes that have attracted attention for their role in the etiology of numerous respiratory disorders such as cystic fibrosis, bronchial asthma, and acute hypoxemic respiratory failure. However, information regarding the interrelationship and competition bet...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2019.110706
更新日期:2019-08-01 00:00:00
abstract::The precursor of an RNA molecule from T4-infected E. coli cells (p2Sp1 RNA) has the capacity to cleave itself at specific positions [(UpA (139-140) and CpA (170-171)], within a putative loop and stem structure. This sequence-specific cleavage requires at least a monovalent cation and non-ionic detergents. We studied t...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/s0162-0134(00)00164-1
更新日期:2000-11-01 00:00:00
abstract::Many properties of cytochromes and model systems depend on orientations of axial ligands. In this work, we elucidated the role of porphyrin substituents on orientation of axial ligands in model systems of cytochromes. The orientations of axially coordinated imidazoles and pyridines in crystal structures of model syste...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2005.10.010
更新日期:2006-01-01 00:00:00
abstract::The gallium(III) complex of a new tripodal 3-hydroxy-4-pyridinone (3,4-HP) chelator has been studied in terms of its physico-chemical and in vivo properties aimed at potential application as probe for nuclear imaging. In particular, based on spectrophotometric titrations, the hexa-coordinated (1:1) gallium complex app...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2010.09.012
更新日期:2011-01-01 00:00:00
abstract::A systematic density functional theory study supported by extended X-ray absorption fine structure (EXAFS) and infrared spectroscopic data was conducted to elucidate how structure and vibrational spectra of aqueous desferrioxamine B (DFOB) metal complexes vary with the metal ion identity. Structural parameters derived...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2013.08.008
更新日期:2013-12-01 00:00:00
abstract::Binary as well as ternary complexes of Zn(II) with diphenylamine-2,2'-dicarboxylic acid (dpdc), diphenylamine-2-amino-2'-carboxylic acid (dpac), diphenylamine-2-hydroxy-2'-carboxylic acid (dphc), diphenylamine-2-mercapto-2'-carboxylic acid (dpmc), and N-(2-pyridino) anthranilic acid (npa) have been synthesized and cha...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(87)80029-6
更新日期:1987-03-01 00:00:00
abstract::Twenty-seven sheep given either copper (Cu) and/or tetrathiomolybdate (TM) were used to study the subcellular distribution of Cu within the kidney and to monitor the location of lysosomes within the subcellular fractions using acid phosphatase (AP) as a marker enzyme. Copper dosing alone increased the Cu content in th...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(89)84003-6
更新日期:1989-01-01 00:00:00
abstract::In this study we report the synthesis, characterization and a thorough biological evaluation of twelve organoruthenium-8-hydroxyquinolinato (Ru-hq) complexes. The chosen hqH ligands bear various halogen atoms in different positions which enables to study effect of the substituents on physico-chemical and biological pr...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2018.05.009
更新日期:2018-09-01 00:00:00
abstract::Prion diseases are neurodegenerative disorders associated with a conformational change of the normal cellular isoform of the prion protein (PrP(C)) to an abnormal scrapie isoform (PrP(Sc)). human prion protein (hPrP(C)) is able to bind up to six Cu(II) ions. Four of them are distributed in the octarepeat domain, conta...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2015.11.015
更新日期:2016-02-01 00:00:00
abstract::Aiming at tumor targeting delivery of oxaliplatin using polymer therapy, a new monomeric platinum(II) complex (dach)Pt[HEDM] (dach: trans-(±)-1,2-diaminocyclohexane; HEDM: 2-hydroxyethoxydiethylmalate) was designed to include the antitumor moiety (dach)Pt and HEDM as a linker to the polyphosphazene backbone. This mono...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2014.06.014
更新日期:2014-11-01 00:00:00
abstract::Copper(II) complexes of the peptide fragment (Dpl122-130) encompassing the sequence 122-130 of human doppel protein were characterized by potentiometric, UV-Visible, CD and EPR spectroscopic methods. An analogous peptide, in which the aspartate residue was substituted by an asparagine amino acid, was synthesized in or...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2009.01.017
更新日期:2009-05-01 00:00:00
abstract::Effect of dietary selenium as sodium selenite on in vivo hematological parameters of Sprague-Dawley rats was examined over a 7-month period. Dietary selenium did not alter total hemoglobin, hematocrits, erythrocyte counts, or the osmotic fragility pattern of rat blood. Selenium-excessive (1.0 ppm) rats showed slightly...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(84)80025-2
更新日期:1984-11-01 00:00:00
abstract::The relationship between respiratory and neurological effects of exposure to aluminium (Al) was investigated in a group of foundry workers exposed to Al at concentrations below the threshold limit value (TLV) binding in Poland (2.0 mg Al2O3 m(-3)). Neurological and neurophysiological parameters indicated subclinical e...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2005.06.027
更新日期:2005-09-01 00:00:00
abstract::Four related ruthenium(III) complexes, with the formula mer-[RuCl(3)(dmso)(N-N)] (dmso=dimethyl sulfoxide; N-N=2,2'-bipyridine (1), 1,10-phenantroline (2), dipyrido[3,2-f:2',3'-h]quinoxaline (3) and dipyrido[3,2-a:2',3'-c]phenazine (4)), have been reported. Complexes 3 and 4 are newly synthesized and characterized by ...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2008.03.005
更新日期:2008-08-01 00:00:00
abstract::Reactions of bacterial Fe(III) cyt b562, HbO2, met Hb and met Mb with Et3PAuCl and Et3PAuNO3 (and some related complexes) have been investigated by electronic absorption and EPR and NMR spectroscopy. Except for met Hb, which denatured, the products were novel high-spin Fe(III) heme proteins. The reactions of cyt b562 ...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(86)80104-0
更新日期:1986-05-01 00:00:00
abstract::The rates at which phosphonocarboxylate and diphosphonate ligands remove iron from the serum iron transport protein transferrin at 25 degrees C and pH 7.4 have been evaluated. These ligands show a combination of saturation and first-order kinetics with respect to the free ligand concentrations. The ability of the liga...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2004.08.008
更新日期:2004-11-01 00:00:00
abstract::Copper is an essential metal ion to many living organisms, including mammals, as it mediates a wide variety of important biochemical processes. At elevated concentrations, copper is extremely toxic to host cells. This paradoxical nature of copper has necessitated a highly regulated procedure for its cellular accumulat...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/s0162-0134(96)00216-4
更新日期:1997-06-01 00:00:00
abstract::The [Cu(sulfathiazolato)(2)(benzimidazole)(2)]2MeOH complex has been synthesised and characterised. It crystallises in the monoclinic system, space group C1c1, with unit cell dimensions a=18.829(7) A, b=12.206(3) A, c=17.233(5) A, alpha=90.06(2) degrees, beta=97.28(3) degrees, gamma=90.21(3) degrees and Z=4. The geome...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/s0162-0134(01)00369-5
更新日期:2002-04-10 00:00:00
abstract::A series of new heterometallic gold(I) thiolates containing ferrocenyl-phoshines were synthesized. Their antimicrobial properties were studied and compared to that of FDA-approved drug, auranofin (Ridaura), prescribed for the treatment of rheumatoid arthritis. MIC in the order of one digit micromolar were found for mo...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2014.05.008
更新日期:2014-09-01 00:00:00
abstract::Rat kidney selenium (Se)-containing proteins were studied by isotopic labeling with [75Se]selenite or [75Se]selenomethionine via three routes: oral, intraperitoneal injection, and incubation of kidney slices with the isotope. The two major Se-containing proteins in kidney were fractionated and partially characterized....
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(88)80005-9
更新日期:1988-08-01 00:00:00
abstract::Interactions of three Ru(II) chlorophenyl terpyridine complexes: [Ru(Cl-Ph-tpy)(en)Cl]Cl (1), [Ru(Cl-Ph-tpy)(dach)Cl]Cl (2) and [Ru(Cl-Ph-tpy)(bpy)Cl]Cl (3) (Cl-Ph-tpy = 4'-(4-chlorophenyl)-2,2':6',2''-terpyridine, en = 1,2-diaminoethane, dach = 1,2-diaminocyclohexane, bpy = 2,2'-bipyridine) with human serum albumin (...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2020.111090
更新日期:2020-07-01 00:00:00
abstract::Novel bismuth(III) complexes 1-4 with the tridentate thiosemicarbazone ligand of 2N1S donor atoms [Hmtsc (L1); 2-acetylpyridine (4N-morpholyl thiosemicarbazone)], the pentadentate double-armed thiosemicarbazone ligand of 3N2S donor atoms [H2dmtsc (L3); 2,6-diacetylpyridine bis(4N-morpholyl thiosemicarbazone)] and the ...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2004.01.011
更新日期:2004-04-01 00:00:00
abstract::The hypothesis that the recent rapid evolution of primate cytochromes c, which primarily involves residues in the least stable Ω-loop (Ω-loop C, residues 40-57), stabilizes the heme crevice of cytochrome c relative to other mammals, is tested. To accomplish this goal, we have compared the properties of human and spide...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2015.12.025
更新日期:2016-05-01 00:00:00
abstract::Deposition of beta sheets of islet amyloid polypeptide (IAPP) in pancreatic tissue is implicated in the aetiology of type 2 diabetes mellitus (T2DM). IAPP is cleaved from its precursor protein, pro-islet amyloid polypeptide (ProIAPP) and incomplete cleavage results in ProIAPP(1-48), which is found co-deposited with IA...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2010.05.012
更新日期:2010-10-01 00:00:00
abstract::The present Mössbauer spectroscopic studies of isolated bacterioferritin and whole cells of Pseudomonas aeruginosa have shown that the iron core of bacterioferritin is not altered on isolation. These studies have also shown that the bacterioferritin core is typically 85% oxidized within the cell and may contain a sign...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/0162-0134(91)80046-k
更新日期:1991-09-01 00:00:00
abstract::The effects exerted by the new complex cis-dichloro-1,2-propylenediaminetetraacetato ruthenium (III), H[RuCl(2)(PDTA-H(2))] [1, RAP], on DNA and cultured tumor cells (ovarian carcinoma TG cell line) were studied. The comparative study of circular dichroism (CD) spectra obtained from DNA and RAP-DNA system evidences th...
journal_title:Journal of inorganic biochemistry
pub_type: 杂志文章
doi:10.1016/j.jinorgbio.2006.07.012
更新日期:2006-11-01 00:00:00