Editorial
03 April 2025
Isabel Correia
and
Sylvia M. Draper
Editorial: New developments in bioinorganic and bioorganic chemistry
Editors
3
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Mini Review
31 January 2024
Can Mn coordination compounds be good candidates for medical applications?
Sandra Kozieł
, 3 more and
Urszula K. Komarnicka
Metal centres provide unique foci for varied biological modes of action that often but not exclusively involve redox or metal-ligand reactions. Metal complexes offer alternative and flexible coordination geometries, electron and proton transfer sites, inner and outer sphere reactivities, sites for redox-active, hemi-labile, and non-innocent ligands, and a variety of potentially controllable properties for exploitation in a therapeutic or biological context. The discovery of the first anticancer, the metal-based compound cisplatin in 1965 by Barnett Rosenberg was a historical outstanding breakthrough and led to a new area of metal-drug discovery. Some metal-based compounds have FDA approval for clinical use, while some undergo clinical trials for various medical therapies. This mini-review focuses on recent progress on Mn-based complexes with potential anticancer, antibacterial, and antifungal activities.
Original Research
10 September 2024
Laura Slappendel
, 3 more and
Shana J. Sturla
582 views
0 citations
![(A) EPR spectra measured at 100 K of 3 mM solutions in DMSO of compounds [VIVO(L–H)(mpo)] measured at 100 K in DMSO solution; (B) Experimental and simulated EPR spectra of [VIVO(L2–H)(mpo)].](https://www.frontiersin.org/_rtmag/_next/image?url=https%3A%2F%2Fwww.frontiersin.org%2Ffiles%2FArticles%2F1304571%2Ffchbi-02-1304571-HTML%2Fimage_m%2Ffchbi-02-1304571-g002.jpg&w=3840&q=75)
Original Research
16 January 2024
Facing diseases caused by trypanosomatid parasites: rational design of multifunctional oxidovanadium(IV) complexes with bioactive ligands
Gonzalo Scalese
, 6 more and
Dinorah Gambino
Searching for new prospective drugs against Chagas disease (American trypanosomiasis) and Leishmaniasis, a series of five heteroleptic vanadium compounds, [VIVO(L-H)(mpo)], where L are 8-hydroxyquinoline derivatives and mpo is 2-mercaptopyridine N-oxide, are synthesized and characterized. Comprehensive characterizations are conducted in solid state and in solution. The compounds are evaluated on epimastigotes and trypomastigotes of Trypanosoma cruzi and in promastigotes of Leishmania infantum, alongside on VERO cells, as a mammalian cell model. The compounds exhibit activity against both forms of T. cruzi and promastigotes of L. infantum, with the trypomastigote infective stage of T. cruzi displaying the highest sensitivity. The most selective vanadium compound [VIVO(L2-H)(mpo)], with L2 = 5-chloro-7-iodo-8-hydroxyquinoline, globally shows adequate selectivity towards the parasite and was selected to carry out further in-depth biological studies. [VIVO(L2-H)(mpo)] significantly impacted the infection potential of cell-derived trypomastigotes and hindered the replication of the T. cruzi amastigote form. Low total vanadium uptake by T. cruzi parasites and preferential accumulation in the soluble proteins fraction, with negligible localization in the DNA fraction, are determined. A trypanocide effect is observed across various concentrations of the compound. The generation of oxidative stress and the induction of mitochondria-dependent apoptosis are proposed as the main mechanisms of the parasite’s death by the VIVO compounds. Both theoretical predictions and experimental data support the hypothesis that inhibiting the parasite-specific enzyme NADH-fumarate reductase activity plays a crucial role in the trypanocidal action of these complexes. Globally, [VIVO(L-H)(mpo)] complexes could be considered interesting anti-T. cruzi agents that deserve further research.
Original Research
11 October 2023
Noemi Carosella
, 4 more and
Stefano Ciurli
Introduction: Urease is an enzyme exploited by many virulent bacteria and fungi to infect the host and exert their virulence. The Gram-negative bacterium Helicobacter pylori relies on the activity of urease to infect the highly acidic human stomach. The activity of urease depends on the presence of a catalytic site containing two Ni(II) ions. In vivo, urease is initially synthesized as an inactive apo-enzyme and requires a post-translational activation process that involves the incorporation of the metal ions into its buried active site. In H. pylori, as well as in other bacteria, this activation process is mediated by four accessory proteins, named UreD, UreF, UreG, and UreE. Targeting the interactions between urease chaperones could potentially inhibit the activation of urease through blocking the Ni(II) ions incorporation, providing a route for the development of antimicrobial strategies against ureolytic pathogens.
Methods: In this paper, an evolutionary couplings (EC) approach was adopted to determine the interaction surface between urease and UreD, the first protein that binds the enzyme, preparing it for the subsequent activation steps. Site-directed mutagenesis and an in-cell assay were used to detect urease activity in recombinant bacteria expressing the mutated operon. The obtained data were used to drive a protein-protein docking computational approach.
Results and Discussion: The EC prediction retrieved ten pairs of residues lying at the interface between UreD and the urease subunit UreB, likely involved in contacts essential to build the protein complex. These contacts were largely confirmed experimentally, leading to the obtainment of a model for the urease-UreD complex that agrees well with the recently reported experimental cryo-EM structure. This work represents a proof of concept for the calculation of reliable models of protein interaction surfaces in the absence of experimental structures of critical assemblies.