Siderophores and metallophores: Metal complexation weapons to fight environmental pollution.

Siderophores are small molecules of organic nature, released by bacteria to chelate iron from the surrounding environment and subsequently incorporate it into the cytoplasm. In addition to iron, these secondary metabolites can complex with a wide variety of metals, which is why they are commonly studied in the environment. Heavy metals can be very toxic when present in large amounts on the planet, affecting public health and all living organisms. The pollution caused by these toxic metals is increasing, and therefore it is urgent to find practical, sustainable, and economical solutions for remediation. One of the strategies is siderophore-assisted bioremediation, an innovative and advantageous alternative for various environmental applications. This research highlights the various uses of siderophores and metallophores in the environment, underscoring their significance to ecosystems. The study delves into the utilization of siderophores and metallophores in both marine and terrestrial settings (e.g. bioremediation, biocontrol of pathogens, and plant growth promotion), such as bioremediation, biocontrol of pathogens, and plant growth promotion, providing context for the different instances outlined in the existing literature and highlighting their relevance in each field. The study delves into the structures and types of siderophores focusing on their singular characteristics for each application and methodologies used. Focusing on recent developments over the last two decades, the opportunities and challenges associated with siderophores and metallophores applications in the environment were mapped to arm researchers in the fight against environmental pollution.

Effect of Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones in the Virulence of Resistant Bacteria.

Drug resistance is rising to alarming levels, constituting one of the major threats to global health. The overexpression of efflux pumps and the formation of biofilms constitute two of the most common resistance mechanisms, favoring the virulence of bacteria. Therefore, the research and development of effective antimicrobial agents that can also counteract resistance mechanisms are extremely important. Pyrazino[2,1-b]quinazoline-3,6-diones, from marine and terrestrial organisms and simpler synthetic analogues, were recently disclosed by us as having relevant antimicrobial properties. In this study, using a multi-step approach, it was possible to synthesize new pyrazino[2,1-b]quinazoline-3,6-diones focusing on compounds with fluorine substituents since, to the best of our knowledge, the synthesis of fluorinated fumiquinazoline derivatives had not been attempted before. The new synthesized derivatives were screened for antibacterial activity and, along with previously synthetized pyrazino[2,1-b]quinazoline-3,6-diones, were characterized for their antibiofilm and efflux-pump-inhibiting effects against representative bacterial species and relevant resistant clinical strains. Several compounds showed relevant antibacterial activity against the tested Gram-positive bacterial species with MIC values in the range of 12.5-77 µM. Furthermore, some derivatives showed promising results as antibiofilm agents in a crystal violet assay. The results of the ethidium bromide accumulation assay suggested that some compounds could potentially inhibit bacterial efflux pumps.

Emerging Target-Directed Approaches for the Treatment and Diagnosis of Microbial Infections.

With the rising levels of drug resistance, developing efficient antimicrobial therapies has become a priority. A promising strategy is the conjugation of antibiotics with relevant moieties that can potentiate their activity by target-directing. The conjugation of siderophores with antibiotics allows them to act as Trojan horses by hijacking the microorganisms' highly developed iron transport systems and using them to carry the antibiotic into the cell. Through the analysis of relevant examples of the past decade, this Perspective aims to reveal the potential of siderophore-antibiotic Trojan horses for the treatment of infections and the role of siderophores in diagnostic techniques. Other conjugated molecules will be the subject of discussion, namely those involving vitamin B12, carbohydrates, and amino acids, as well as conjugated compounds targeting protein degradation and ß-lactamase activated prodrugs.

Highly Porous Composite Scaffolds Endowed with Antibacterial Activity for Multifunctional Grafts in Bone Repair.

The present study deals with the development of multifunctional biphasic calcium phosphate (BCP) scaffolds coated with biopolymers-poly(ε-caprolactone) (PCL) or poly(ester urea) (PEU)-loaded with an antibiotic drug, Rifampicin (RFP). The amounts of RFP incorporated into the PCL and PEU-coated scaffolds were 0.55 ± 0.04 and 0.45 ± 0.02 wt%, respectively. The in vitro drug release profiles in phosphate buffered saline over 6 days were characterized by a burst release within the first 8h, followed by a sustained release. The Korsmeyer-Peppas model showed that RFP release was controlled by polymer-specific non-Fickian diffusion. A faster burst release (67.33 ± 1.48%) was observed for the PCL-coated samples, in comparison to that measured (47.23 ± 0.31%) for the PEU-coated samples. The growth inhibitory activity against Escherichia coli and Staphylococcus aureus was evaluated. Although the RFP-loaded scaffolds were effective in reducing bacterial growth for both strains, their effectiveness depends on the particular bacterial strain, as well as on the type of polymer coating, since it rules the drug release behavior. The low antibacterial activity demonstrated by the BCP-PEU-RFP scaffold against E. coli could be a consequence of the lower amount of RFP that is released from this scaffold, when compared with BCP-PCL-RFP. In vitro studies showed excellent cytocompatibility, adherence, and proliferation of human mesenchymal stem cells on the BCP-PEU-RFP scaffold surface. The fabricated highly porous scaffolds that could act as an antibiotic delivery system have great potential for applications in bone regeneration and tissue engineering, while preventing bacterial infections.

Tryptophan derived natural marine alkaloids and synthetic derivatives as promising antimicrobial agents.

Antimicrobial resistance has become a major threat to public health worldwide, as pathogenic microorganisms are finding ways to evade all known antimicrobials. Therefore, the demand for new and effective antimicrobial agents is also increasing. Natural products have always played an important role in drug discovery, either by themselves or as inspiration for synthetic compounds. The marine environment is a rich source of bioactive metabolites, and among them, tryptophan-derived alkaloids stand out for their abundance and by displaying a variety of biological activities, with antimicrobial properties being among the most significant. This review aims to reveal the potential of marine alkaloids derived from tryptophan as antimicrobial agents. Relevant examples of these compounds and their synthetic analogues reported in the last decades are presented and discussed in detail, with their mechanism of action and synthetic approaches whenever relevant. Several tryptophan-derived marine alkaloids have shown potent and promising antimicrobial activities, whether against bacteria, fungi, or virus. Synthetic approaches to many of the compounds have been developed and recent methodologies are proving to be efficient. Even though most of the studies regarding the antimicrobial activity are still preliminary, this class of compounds has proven to be worth of further investigation and may provide useful lead compounds for the development of antimicrobial agents. Overall, marine alkaloids derived from tryptophan are revealed as a valuable class of antimicrobials and molecular modifications in order to reduce the toxicity of these compounds and additional studies regarding their mechanism of action are interesting topics to explore in the future.

Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging.

Antioxidants have long been used in the cosmetic industry to prevent skin photoaging, which is mediated by oxidative stress, making the search for new antioxidant compounds highly desirable in this field. Naturally occurring xanthones are polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. This class of polyphenols has a privileged scaffold that grants them several biological activities. We have previously identified simple oxygenated xanthones as promising antioxidants and disclosed as hit, 1,2-dihydroxyxanthone (1). Herein, we synthesized and studied the potential of xanthones with different polyoxygenated patterns as skin antiphotoaging ingredients. In the DPPH antioxidant assay, two newly synthesized derivatives showed IC50 values in the same range as ascorbic acid. The synthesized xanthones were discovered to be excellent tyrosinase inhibitors and weak to moderate collagenase and elastase inhibitors but no activity was revealed against hyaluronidase. Their metal-chelating effect (FeCl3 and CuCl2) as well as their stability at different pH values were characterized to understand their potential to be used as future cosmetic active agents. Among the synthesized polyoxygenated xanthones, 1,2-dihydroxyxanthone (1) was reinforced as the most promising, exhibiting a dual ability to protect the skin against UV damage by combining antioxidant/metal-chelating properties with UV-filter capacity and revealed to be more stable in the pH range that is close to the pH of the skin. Lastly, the phototoxicity of 1,2-dihydroxyxanthone (1) was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested.

Increasing the Antimicrobial Activity of Amphiphilic Cationic Copolymers by the Facile Synthesis of High Molecular Weight Stars by Supplemental Activator and Reducing Agent Atom Transfer Radical Polymerization.

Infections caused by bacteria represent a great motif of concern in the health area. Therefore, there is a huge demand for more efficient antimicrobial agents. Antimicrobial polymers have attracted special attention as promising materials to prevent infectious diseases. In this study, a new polymeric system exhibiting antimicrobial activity against a range of Gram-positive and Gram-negative bacterial strains at micromolar concentrations (e.g., 0.8 µM) was developed. Controlled linear and star-shaped copolymers, comprising hydrophobic poly(butyl acrylate) (PBA) and cationic poly(3-acrylamidopropyl)trimethylammonium chloride) (PAMPTMA) segments, were obtained by supplemental activator and reducing agent atom transfer radical polymerization (SARA ATRP) at 30 °C. The antibacterial activity of the polymers was studied by varying systematically the molecular weight (MW), hydrophilic/hydrophobic balance, and architecture. The MW was found to exert the greatest influence on the antimicrobial activity of the polymers, with minimum inhibitory concentration values decreasing with increasing MW. Live/dead membrane integrity assays and scanning electron microscopy analysis confirmed the bactericidal character of the synthesized PAMPTMA- (b)co-PBA polymers.