Metal-Based Compounds as Prospective Antileishmanial Agents: Inhibition of Trypanothione Reductase by Selected Gold Complexes

ChemMedChem ◽  
2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Gianni Colotti ◽  
Andrea Ilari ◽  
Annarita Fiorillo ◽  
Paola Baiocco ◽  
Maria Agostina Cinellu ◽  
...  
Keyword(s):  
Trypanothione Reductase ◽  
Gold Complexes

scholarly journals Preclinical Gold Complexes as Oral Drug Candidates to Treat Leishmaniasis Are Potent Trypanothione Reductase Inhibitors

2020 ◽  
Vol 6 (5) ◽  
pp. 1121-1139 ◽  
Author(s):  
Luiza G. Tunes ◽  
Roberta E. Morato ◽  
Adriana Garcia ◽  
Vinicius Schmitz ◽  
Mario Steindel ◽  
...  
Keyword(s):  
Oral Drug ◽  
Trypanothione Reductase ◽  
Gold Complexes ◽  
Drug Candidates ◽  
Reductase Inhibitors

Electronmicroscopic localization of ribonucleic acids in ciliate Bursaria truncatella during cell division

1990 ◽  
Vol 48 (3) ◽  
pp. 132-133
Author(s):  
Vladimir Popenko ◽  
Natalya Cherny ◽  
Maria Yakovleva
Keyword(s):  
Cell Division ◽  
High Specificity ◽  
Longitudinal Axis ◽  
Gold Complexes ◽  
Somatic Nucleus ◽  
Ribonucleic Acids ◽  
Biological Meaning ◽  
Bivalent Cations ◽  
Lowicryl K4m ◽  
Short Time

Highly polyploid somatic nucleus (macronucleus) of ciliate Bursaria truncatella under goes severe changes in morphology during cell division. At first, macronucleus (Ma) condences, diminishes in size and turns perpendicular to longitudinal axis of the cell. After short time, Ma turns again, elongates and only afterwards the process of division itself occurs. The biological meaning of these phenomena is not clear.Localization of RNA in the cells was performed on sections of ciliates B. truncatella, embedded in “Lowicryl K4M” at various stages: (1) before cell division (Figs. 2,3); (11) at the stage of macronucleus condensation; (111) during elongation of Ma (Fig.4); (1111) in young cells (0-5min. after division). For cytochemical labelling we used RNaseAcolloidal gold complexes (RNase-Au), which are known to bind to RNA containing cell ularstructures with high specificity. The influence of different parameters on the reliability and reproducibility of labelling was studied. In addition to the factors, discussed elsewhere, we found that the balance of mono- and bivalent cations is of great significance.

Novel Scaffolds for Leishmania infantum Trypanothione Reductase Inhibitors Derived from Brazilian Natural Products Biodiversity

2021 ◽  
Vol 18 (4) ◽  
pp. 398-418
Author(s):  
Vinícius Guimarães da Paixão ◽  
Samuel Silva da Rocha Pita
Keyword(s):  
Natural Products ◽  
Leishmania Infantum ◽  
In Vitro Assays ◽  
Current Therapy ◽  
Pharmacokinetic Analysis ◽  
Trypanothione Reductase ◽  
Resistant Species ◽  
Reductase Inhibitors ◽  
Thiol Redox

Background: Leishmania infantum causes the most lethal form of Leishmaniasis: Visceral leishmaniasis. Current therapy for this disease is related to the development of drug-resistant species and toxicity. Trypanothione Reductase (LiTR), a validated target for the drug discovery process, is involved with parasites' thiol-redox metabolism. Objective: In this study, through Virtual Screening employing two distinct Natural Products Brazilian databases, we aimed to identify novel inhibitor scaffolds against LiTR. Results: Thus, the “top 10” LiTR-ligand energies have been selected and their interaction profiles into LiTR sites through the AuPosSOM server have been verified. Finally, Pred-hERG, Aggregator Advisor, FAF-DRUGS, pkCSM and DataWarrior were employed and their results allowed us to evaluate, respectively, the cardiotoxicity, aggregation capacity, presence of false-positive compounds (PAINS) and their toxicities. Conclusion: Three molecules that overcame the in silico pharmacokinetic analysis and have a good interaction with LiTR, were chosen to use in vitro assays hoping that our computational results reported here would aid the development of new anti-leishmanial compounds.

scholarly journals Emerging Molecular Receptors for the Specific-Target Delivery of Ruthenium and Gold Complexes into Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3153
Author(s):  
João Franco Machado ◽  
João D. G. Correia ◽  
Tânia S. Morais
Keyword(s):  
Progesterone Receptors ◽  
Biological Evaluation ◽  
Cell Organelles ◽  
Gold Complexes ◽  
Main Research ◽  
Wide Range ◽  
Cancer Types ◽  
Organometallic Molecules ◽  
G Protein Coupled

Cisplatin and derivatives are highly effective in the treatment of a wide range of cancer types; however, these metallodrugs display low selectivity, leading to severe side effects. Additionally, their administration often results in the development of chemoresistance, which ultimately results in therapeutic failure. This scenario triggered the study of other transition metals with innovative pharmacological profiles as alternatives to platinum, ruthenium- (e.g., KP1339 and NAMI-A) and gold-based (e.g., Auranofin) complexes being among the most advanced in terms of clinical evaluation. Concerning the importance of improving the in vivo selectivity of metal complexes and the current relevance of ruthenium and gold metals, this review article aims to survey the main research efforts made in the past few years toward the design and biological evaluation of target-specific ruthenium and gold complexes. Herein, we give an overview of the inorganic and organometallic molecules conjugated to different biomolecules for targeting membrane proteins, namely cell adhesion molecules, G-protein coupled receptors, and growth factor receptors. Complexes that recognize the progesterone receptors or other targets involved in metabolic pathways such as glucose transporters are discussed as well. Finally, we describe some complexes aimed at recognizing cell organelles or compartments, mitochondria being the most explored. The few complexes addressing targeted gene therapy are also presented and discussed.

Gold complexes of bis-indazole-derived N-Heterocyclic carbene: Synthesis, structural characterizations, and catalysis

2021 ◽  
Vol 1233 ◽  
pp. 130043
Author(s):  
Hua Zhang ◽  
Ting Xu ◽  
Dongdong Li ◽  
Tao Cheng ◽  
Jing Chen ◽  
...  
Keyword(s):  
Gold Complexes ◽  
Structural Characterizations

Betraying the Parasite’s Redox System: Diaryl Sulfide-Based Inhibitors of Trypanothione Reductase: Subversive Substrates and Antitrypanosomal Properties

ChemMedChem ◽  
2007 ◽  
Vol 2 (12) ◽  
pp. 1708-1712 ◽  
Author(s):  
Bernhard Stump ◽  
Marcel Kaiser ◽  
Reto Brun ◽  
R. Luise Krauth-Siegel ◽  
François Diederich
Keyword(s):  
Redox System ◽  
Trypanothione Reductase ◽  
Diaryl Sulfide
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