Zinc(II)-Dipicolylamine Coordination Complexes as Targeting and Chemotherapeutic Agents for Leishmania major

Rice, Douglas R.; Vacchina, Paola; Norris-Mullins, Brianna; Morales, Miguel A.; Smith, Bradley D.

doi:10.1128/aac.00410-16

Cited by 24 publications

(14 citation statements)

References 55 publications

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“…45,46 Zn(II) complexes featuring the 2-picolylamine binding motif have been recently reported to inhibit the growth of L. major, with good activity in vivo. 47 We found that the hydrolysis products from complex 8, namely Zn(II) complex 9, also showed anti-parasitic activity to some extent (17.1 μM). Several modes of action for Zn(II) complexes with anti-leishmanial properties have been discussed in the literature: some compounds have been reported to inhibit enzymes essential for the parasite's carbohydrate metabolism, such as those involved in the Embden-Meyerhof pathway.…”

Section: -Esi †)mentioning

confidence: 79%

Glycosylated metal chelators as anti-parasitic agents with tunable selectivity

et al. 2017

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Trypanosoma cruzi and Leishmania amazonensis are the causative agents of Chagas' disease and leishmaniasis, respectively. These conditions affect millions of people worldwide, especially in developing countries. As such, there is an urgent need for novel, efficient and cost-effective treatments for these diseases, given the growing resistance and side-effects of current therapies. This work details the synthesis and evaluation of the anti-parasitic activity of novel amino- and iminopyridyl metal chelators, their glycosylated derivatives and some of their metal complexes. Our results revealed the potent and metal-dependent activity for the aminopyridyl compounds: Cu(ii) complexes were most effective against T. cruzi trypomastigotes, while Zn(ii) complexes presented excellent activity against L. amazonensis promastigotes. In addition, the compounds showed excellent selectivity indexes and very low relative toxicity as judged by in vitro and in vivo studies, respectively, using RAW macrophages and Galleria mellonella larvae model.

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Section: -Esi †)mentioning

confidence: 79%

Glycosylated metal chelators as anti-parasitic agents with tunable selectivity

et al. 2017

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“…Clearance of the divalent tracer from the bloodstream was, compared to monovalent tracers, slow and mainly through the liver, gall bladder and intestines. Because of exposure of negatively charged molecules however, in other studies 99m Tc-HYNIC-DPA was shown to image cell death in vivo [123], cardiomyocyte apoptosis [125], mammary and prostate tumours [126], and more recently Leishmania major parasites [127]. Because of the electrostatic interaction with charged groups within tumour cell membranes and necrotic tissues limits its use for specific imaging of infections [128].…”

Section: Imaging Of the Bacterial Membranementioning

confidence: 99%

An update on radiotracer development for molecular imaging of bacterial infections

Welling

Hensbergen

Bunschoten

et al. 2019

Clin Transl Imaging

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Background Bacterial infections are still a major global healthcare problem. To combat the increasing antimicrobial resistance, early diagnosis of bacterial infections-including the identification of bacterial species-is needed to improve antibiotic stewardship and to help reduce the use of broad-spectrum antibiotics. To aid successful targeted antibiotic treatment, specific detection and localisation of infectious organisms is warranted. Nuclear medicine imaging approaches have been successfully used to diagnose bacterial infections and to differentiate between pathogen induced infections and sterile inflammatory processes. Aim In this comprehensive review we present an overview of recent developments in radiolabelled bacterial imaging tracers. Methods The PubMed/MEDLINE and Embase (OvidSP) literature databases were systematically searched for publications on SPECT and PET on specific imaging of bacterial using specific guidelines with MeSH-terms, truncations, and completion using cross-references. Tracers in literature that was extensively reviewed before 2016 were not included in this update. Where possible, the chemical structure of the radiolabelled compounds and clinical images were shown. Results In 219 original articles pre-clinical and clinical imaging of bacterial infection with new tracers were included. In our view, the highest translational potential lies with tracers that are specific to target the pathogens: e.g., 99m Tc-and 68 Galabelled UBI 29-41 , 99m Tc-vancomycin, m-[ 18 F]-fluoro-PABA, [methyl-11 C]-D-methionine, [ 18 F]-FDS, [ 18 F]-maltohexaose and [ 18 F]-maltotriose. An encouraging note is that some of these tracers have already been successfully evaluated in clinical settings. Conclusion This review summarises updates in tracer development for specific (pre-clinical and clinical) imaging of bacterial infections. We propsed some promising tracers that are likely to become innovative standards in the clinical setting in the near feature.

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“…ZnDPA targeting of iRBC was explored using the green fluorescent probe mSeek which was shown previously to stain bacteria and Leishmania parasites. [27, 30] Samples of red blood cells (10 4 cells per mL) infected with P. Falciparum W2 were treated with Hoechst nuclear stain which selectively localizes to iRBCs through binding parasite DNA. The same samples were co-treated with mSeek (5 μM) in HEPES buffer.…”

Section: Resultsmentioning

confidence: 99%

“…[26] Recently, we discovered that ZnDPA complexes selectively target and kill the trypanosomatid parasite Leishmania major ( L. major ), a causative agent of cutaneous leishmaniasis. [27] The surface of Leishmania parasites is negatively charged due to high fractions of anionic lipids and a thick coating of the anionic polysaccharide lipophosphoglycan. In vivo treatment efficacy studies showed that a ZnDPA treatment regimen significantly reduced parasite burden with minimal side effects to the local host tissue.…”

Section: Introductionmentioning

confidence: 99%

Antiplasmodial activity of targeted zinc(II)-dipicolylamine complexes

Rice

Betancourt-Mendiola

Murillo-Solano

et al. 2017

Bioorganic & Medicinal Chemistry

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This study measured the antiplasmodial activity of nine zinc-dipicolylamine (ZnDPA) complexes against three strains of Plasmodium falciparum, the causative parasite of malaria. Growth inhibition assays showed significant activity against all tested strains, with 50% inhibitory concentrations between 5 and 600 nM and almost no toxic effect against host cells including healthy red blood cells. Fluorescence microscopy studies with a green-fluorescent ZnDPA probe showed selective targeting of infected red blood cells. The results suggest that ZnDPA coordination complexes are promising antiplasmodial agents with potential for targeted malaria treatment.

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Zinc(II)-Dipicolylamine Coordination Complexes as Targeting and Chemotherapeutic Agents for Leishmania major

Cited by 24 publications

References 55 publications

Glycosylated metal chelators as anti-parasitic agents with tunable selectivity

Glycosylated metal chelators as anti-parasitic agents with tunable selectivity

An update on radiotracer development for molecular imaging of bacterial infections

Antiplasmodial activity of targeted zinc(II)-dipicolylamine complexes

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