Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Rational approaches towards inorganic and organometallic antibacterials.

ABSTRACT: The occurrence of drug-resistant bacteria is drastically rising and new and effective antibiotic classes are urgently needed. However, most of the compounds in development are minor modifications of previously used drugs to which bacteria can easily develop resistance. The investigation of inorganic and organometallic compounds as antibiotics is an alternative approach that holds great promises due to the ability of such molecules to trigger metal-specific mechanisms of action, which results in lethal consequences for pathogens. In this review, a selection of concepts to rationally design inorganic and organometallic antibiotics is discussed, highlighting their advantages by comparing them to classical drug discovery programmes. The review concludes with a short perspective for the future of antibiotic drug development and the role metal-based compounds will play in the field.

SUBMITTER: Hess J

PROVIDER: S-EPMC8997702 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Rational approaches towards inorganic and organometallic antibacterials.

Hess Jeannine J

Biological chemistry 20210713 4

The occurrence of drug-resistant bacteria is drastically rising and new and effective antibiotic classes are urgently needed. However, most of the compounds in development are minor modifications of previously used drugs to which bacteria can easily develop resistance. The investigation of inorganic and organometallic compounds as antibiotics is an alternative approach that holds great promises due to the ability of such molecules to trigger metal-specific mechanisms of action, which results in ...[more]

PMID: 34253000

Similar Datasets

Preparation and Antitumoral Activity of Au-Based Inorganic-Organometallic Nanocomposites.

Project description:The synergy between gelator molecules and nanostructured materials is currently a novel matter of study. The possibility to carefully design the skeleton of the molecular entity as well as the nanostructure's morphological and chemical features offers the possibility to prepare a huge variety of nanocomposites with properties potentially different than just the sum of those of the individual building blocks. Here we describe the synthesis and characterization of nanocomposites made by the unconventional combination of phosphine-Au(I)-alkynyl-based organometallic gelating molecules and plasmonic Au nanoparticles. Our results indicate that the interaction between the two moieties leads to a significant degree of aggregation in both hydrophilic and hydrophobic media, either when using DAPTA or PTA-based organometallic molecules, with the formation of a sponge-like hybrid powder upon solvent evaporation. The biological activity of the nanocomposites was assessed, suggesting the existence of a synergetic effect evidenced by the higher cytotoxicity of the hybrid systems with respect to that of any of their isolated counterparts. These results represent a preliminary proof-of-concept for the exploitation of these novel nanocomposites in the biomedical field.

| S-EPMC6375849 | biostudies-literature

Co-crystallization of antibacterials with inorganic salts: paving the way to activity enhancement.

Project description:Co-crystallization of the antibacterial agents proflavine and methyl viologen with the inorganic salts CuCl, CuCl2 and AgNO3 results in enhanced antimicrobial activity with respect to the separate components.

| S-EPMC9048849 | biostudies-literature

Chemogenomic approaches to rational drug design.

Project description:Paradigms in drug design and discovery are changing at a significant pace. Concomitant to the sequencing of over 180 several genomes, the high-throughput miniaturization of chemical synthesis and biological evaluation of a multiple compounds on gene/protein expression and function opens the way to global drug-discovery approaches, no more focused on a single target but on an entire family of related proteins or on a full metabolic pathway. Chemogenomics is this emerging research field aimed at systematically studying the biological effect of a wide array of small molecular-weight ligands on a wide array of macromolecular targets. Since the quantity of existing data (compounds, targets and assays) and of produced information (gene/protein expression levels and binding constants) are too large for manual manipulation, information technologies play a crucial role in planning, analysing and predicting chemogenomic data. The present review will focus on predictive in silico chemogenomic approaches to foster rational drug design and derive information from the simultaneous biological evaluation of multiple compounds on multiple targets. State-of-the-art methods for navigating in either ligand or target space will be presented and concrete drug design applications will be mentioned.

| S-EPMC1978269 | biostudies-other

WalK, the Path towards New Antibacterials with Low Potential for Resistance Development.

Project description:Resistance to antibiotics used in the treatment of bacterial infectious diseases is a global health problem. More than a decade ago, two-component systems such as WalKR were proposed as ideal targets for the development of new antibiotics. Biochemical screens for WalKR inhibitors using compound libraries have identified many hits, some of which were shown to have non-specific effects. The recently published structures of the S. mutans and B. subtilis WalK provide the opportunity to study inhibitors of WalK autophosphorylation at the atomic level and means to design compounds with improved specificity and affinity using a structure-based approach.

| S-EPMC4027477 | biostudies-literature

Rational design of inorganic dielectric materials with expected permittivity.

Project description:Techniques for rapid design of dielectric materials with appropriate permittivity for many important technological applications are urgently needed. It is found that functional structure blocks (FSBs) are helpful in rational design of inorganic dielectrics with expected permittivity. To achieve this, coordination polyhedra are parameterized as FSBs and a simple empirical model to evaluate permittivity based on these FSB parameters is proposed. Using this model, a wide range of examples including ferroelectric, high/low permittivity materials are discussed, resulting in several candidate materials for experimental follow-up.

| S-EPMC4663754 | biostudies-literature

An Inorganic Fluorescent Chemosensor: Rational Design and Selective Mg2+ Detection

Project description:A Zn2+ based complex, 3, displays

| S-EPMC9893466 | biostudies-literature

Towards rational graft-versus-host disease prophylaxis.

Project description: Not available

| S-EPMC3590081 | biostudies-literature

Towards Rational Computational Engineering of Psychrophilic Enzymes.

Project description:Cold-adapted enzymes from psychrophilic species achieve their high catalytic efficiency at low temperature by a different partitioning of the activation free energy into its enthalpic and entropic components, compared to orthologous mesophilic enzymes. Their lower activation enthalpy, partly compensated by an increased entropic penalty, has been suggested to originate from changes in flexibility of the protein surface. Multiple sequence alignments of psychrophilic and mesophilic enzymes also show characteristic motifs located in surface loops of the protein. Here, we use computer simulations to examine the effects of a number of designed surface mutations of psychrophilic and mesophilic elastases on the temperature dependence of the catalyzed peptide cleavage reaction. For each of 14 mutant enzyme variants we report calculations of their thermodynamic activation parameters. The results show that substitution of psychrophilic loop residues into the mesophilic enzyme consistently changes both the activation parameters and loop flexibilities towards the former, and vice versa for opposite substitutions.

| S-EPMC6915740 | biostudies-literature

Towards all inorganic antimony sulphide semitransparent solar cells.

Project description:NiO, a wide band gap hole-transporting material (HTM), is gaining attention in photovoltaics due to its optical transparency, chemical stability, and favourable band alignment with absorber. This study uses NiOx nanoparticle-based HTM in semi-transparent Sb2S3 solar cells via a simple chemical precipitation method. We optimised NiOx layer by varying precursor solution concentration and studied its impact on optical and structural properties, composition of nanoparticles and subsequent effect on the performance of semi-transparent Sb2S3 solar cell. NiOx nanoparticles, deposited from nickel(II)nitrate hexahydrate (precursor solution concentrations of 0.2 M to 1.2 M), were thermally treated by two steps at 90 °C for 6 h and 270 °C for 3 h. Nanoparticles with crystallite sizes of 6-9 nm had band gaps (Eg) of ca. 3.65-3.70 eV. Using 1.2 M concentration yielded the largest crystallites (9 nm), lowest Eg (3.65 eV) while retaining the most precursor residues. The highest power conversion efficiency (2.68%) was achieved with NiOx from a 0.5 M precursor, a 60% improvement over HTM-free cells. The effect of precursor solution concentration on the solar cell parameters (efficiency, fill factor, open circuit voltage and short circuit current) are discussed. Present work paves a path toward stable, efficient, and cost-effective all-inorganic Sb2S3 solar cells using NiOx HTM instead of organic counterparts.

| S-EPMC11718080 | biostudies-literature

Rational approaches to improving selectivity in drug design.

Project description: Not available

| S-EPMC3285144 | biostudies-literature