Heteroleptic oxidovanadium(IV) complexes of 2-hydroxynaphtylaldimine and polypyridyl ligands against Trypanosoma cruzi and prostate cancer cells

Scalese, Gonzalo; Mosquillo, M. Florencia; Rostán, Santiago; Castiglioni, Jorge; Alho, Irina; Pérez, Leticia; Correia, Isabel; Marques, Fernanda; Pessoa, João Costa; Gambino, Dinorah

doi:10.1016/j.jinorgbio.2017.07.014

Cited by 33 publications

(15 citation statements)

References 49 publications

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“…Several publications dealing with vanadium complexes for potential antitrypanosomal treatment are available, and some of this work was done by the group of Dinorah Gambino. They proposed several vanadium complexes based on salicylaldehyde-and polypyridyl-derivatives ligands [141][142][143]. Another example is a vanadium complex of aminophen and bromosalycilaldehyde (Figure 18, compound 24), whose IC 50 was shown to be in the low micromolar range (0.27-3.8 µM) [144,145] against T. cruzi, similar to the standard drug nifurtimox, but a live/dead assay only resulted in a trypanostatic effect, with the parasites recovering to normal growth after the cutting off treatment.…”

Section: Vanadiummentioning

confidence: 99%

New Antimicrobial Strategies Based on Metal Complexes

2020

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Traditional organic antimicrobials mainly act on specific biochemical processes such as replication, transcription and translation. However, the emergence and wide spread of microbial resistance is a growing threat for human beings. Therefore, it is highly necessary to design strategies for the development of new drugs in order to target multiple cellular processes that should improve their efficiency against several microorganisms, including bacteria, viruses or fungi. The present review is focused on recent advances and findings of new antimicrobial strategies based on metal complexes. Recent studies indicate that some metal ions cause different types of damages to microbial cells as a result of membrane degradation, protein dysfunction and oxidative stress. These unique modes of action, combined with the wide range of three-dimensional geometries that metal complexes can adopt, make them suitable for the development of new antimicrobial drugs.

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Section: Vanadiummentioning

confidence: 99%

New Antimicrobial Strategies Based on Metal Complexes

2020

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“…Looking for activity against T. cruzi, our group designed oxidovanadium (IV)-based compounds including polypyridyl ligands (NN) with DNA intercalating capacity [16][17][18][19][20][21][22][23]. In particular, a family of 37 structurally related [V IV O(L-2H)(NN)] complexes, including semicarbazones of salicylaldehyde derivatives as coligands L, has turned out to be promising based on its submicromolar half-maximal inhibitory concentration (IC 50 ) range and high selectivity in comparison to mammalian cells.…”

Section: Introductionmentioning

confidence: 99%

High Throughput Approaches to Unravel the Mechanism of Action of a New Vanadium-Based Compound against Trypanosoma cruzi

Mosquillo

Smircich

Lima

et al. 2020

Bioinorganic Chemistry and Applications

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Treatment for Chagas disease, a parasitosis caused by Trypanosoma cruzi, has always been based on two drugs, nifurtimox and benznidazole, despite the toxic side effects described after prolonged prescription. In this work, we study a new prospective antitrypanosomal drug based on vanadium, here named V IV O(5Brsal)(aminophen). We found a good IC 50 value, (3.76 ± 0.08) μM, on CL Brener epimastigotes. e analysis of cell death mechanism allowed us to rule out the implication of a mechanism based on early apoptosis or necrosis. Recovery assays revealed a trypanostatic effect, accompanied by cell shape and motility alterations. An uptake mostly associated with the insoluble fraction of the parasites was deduced through vanadium determinations. Concordantly, no drastic changes of the parasite transcriptome were detected after 6 h of treatment. Instead, proteomic analysis uncovered the modulation of proteins involved in different processes such as energy and redox metabolism, transport systems, detoxifying pathways, ribosomal protein synthesis, and proteasome protein degradation. Overall, the results here presented lead us to propose that V IV O(5Brsal)(aminophen) exerts a trypanostatic effect on T. cruzi affecting parasite insoluble proteins.

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“…Instead, bands at ca. 1620 cm −1 and 1593 cm −1 are observed which are characteristic of a single CO bond typical of the coordination of the ligand enolate form ( Figure S1 ) [ 31 , 32 , 41 , 46 , 50 ]. The simultaneous presence of the semicarbazone ligand L and the 8-hydroxyquinoline derivative co-ligand in the coordination sphere of vanadium led to quite complex spectra, particularly in the 1600–1500 cm −1 region ( Figures S2–S6 ), where bands due to ν(C=C) and ν(C=N) of heterocyclic compounds usually appear.…”

Section: Resultsmentioning

confidence: 99%

“…Different series of V IV O-based compounds bearing activity against T. cruzi were developed by including polypyridyl ligands that have DNA intercalating capacity [ 17 , 21 ]. In particular, heteroleptic compounds including dideprotonated tridentate salicylaldehyde semicarbazones as coligands showed promising results [ 30 , 31 , 32 ]. Later on, the research was expanded by choosing the bidentate 8-hydroxyquinoline scaffold for substituting the NN ligands.…”

Section: Introductionmentioning

confidence: 99%

Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of Trypanosoma cruzi

et al. 2021

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Five heteroleptic compounds, [VVO(IN-2H)(L-H)], where L are 8-hydroxyquinoline derivatives and IN is a Schiff base ligand, were synthesized and characterized in both the solid and solution state. The compounds were evaluated on epimastigotes and trypomastigotes of Trypanosoma cruzi as well as on VERO cells, as a mammalian cell model. Compounds showed activity against trypomastigotes with IC50 values of 0.29–3.02 μM. IN ligand and the new [VVO2(IN-H)] complex showed negligible activity. The most active compound [VVO(IN-2H)(L2-H)], with L2 = 5-chloro-7-iodo-8-hydroxyquinoline, showed good selectivity towards the parasite and was selected to carry out further biological studies. Stability studies suggested a partial decomposition in solution. [VVO(IN-2H)(L2-H)] affects the infection potential of cell-derived trypomastigotes. Low total vanadium uptake by parasites and preferential accumulation in the soluble proteins fraction were determined. A trypanocide effect was observed when incubating epimastigotes with 10 × IC50 values of [VVO(IN-2H)(L2-H)] and the generation of ROS after treatments was suggested. Fluorescence competition measurements with DNA:ethidium bromide adduct showed a moderate DNA interaction of the complexes. In vivo toxicity study on C. elegans model showed no toxicity up to a 100 μM concentration of [VVO(IN-2H)(L2-H)]. This compound could be considered a prospective anti-T. cruzi agent that deserves further research.

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Heteroleptic oxidovanadium(IV) complexes of 2-hydroxynaphtylaldimine and polypyridyl ligands against Trypanosoma cruzi and prostate cancer cells

Cited by 33 publications

References 49 publications

New Antimicrobial Strategies Based on Metal Complexes

New Antimicrobial Strategies Based on Metal Complexes

High Throughput Approaches to Unravel the Mechanism of Action of a New Vanadium-Based Compound against Trypanosoma cruzi

Heteroleptic Oxidovanadium(V) Complexes with Activity against Infective and Non-Infective Stages of Trypanosoma cruzi

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