Siderophore-Conjugated Antifungals: A Strategy to Potentially Cure Fungal Infections.

Fungi pose a global threat to humankind due to the increasing emergence of multi-drug-resistant fungi. There is a rising incidence of invasive fungal infections. Due to the structural complexity of fungal cell membranes, only a few classes of antifungal agents are effective and have been approved by the U.S. FDA. Hence, researchers globally are focusing on developing novel strategies to cure fungal infections. One of the potential strategies is the "Trojan horse" approach, which uses the siderophore-mediated iron acquisition (SIA) system to scavenge iron to deliver potent antifungal agents for therapeutics and diagnostics. These siderophore conjugates chelate to iron and are taken up through siderophore-iron transporters, which are overexpressed exclusively on microbes such as bacteria or fungi, but not mammalian cells. Our comprehensive review delves into recent advancements in the design of siderophore-conjugated antifungal agents to gain fungal cell entry. Notably, our focus extends to unraveling the intricate relationship between the structure of natural siderophores or siderophore-like molecules and the resulting antifungal activity. By exploring these design strategies, we aim to contribute to the ongoing discourse on combating drug-resistant fungal infections and advancing the landscape of antifungal theranostics.

Effective chromium removal of metal anchored alginate-chitosan binary bio-composites.

Water is the most essential resource for the biotic and abiotic components of an ecosystem. Any change in the quality of this water may cause adverse impact on the ecosystem. Hexavalent chromium is one such important pollutant that gets exposed in the water mainly through anthropogenic processes. Adsorption is considered to be an effective, economic and easiest method for remediation of such pollutants. Amongst the innumerable adsorbents available, biopolymers fetch the interest due to its cost effectiveness, efficiency and biocompatibility. But, the mechanical strength and workability of such biopolymers makes it unfit to use as an adsorbent. To improve these drawbacks, synthesis of biopolymeric composites become the need of the hour. So, an attempt was made here to synthesize metal cross-linked binary bio-composites using Alginate and Chitosan polymer matrix. Synthesized bio-composites were characterised with the aid of FTIR, XPS, Thermal analysis, SEM with EDAX and subjected for hexavalent chromium removal from water. Analysis of variance (ANOVA) with 95 % confidence intervals was used to assess the significance of independent variables and their interactions. Adsorption studies were done using batch process and to achieve greater sorption, various influencing parameters were optimized one by one. While investigating one parameter, other parameters were kept unaltered. Optimization was done for the parameters like contact time, dosage of the adsorbent, pH of the medium and presence of co-ions. Contact time and dosage for all the composites was 30 mins and 0.1 g respectively. Amongst the composites, Zirconium loaded binary composite possess high sorption capacity of around 14.8 mg/g. While Calcium and Iron loaded composites exhibit sorption capacity of around 9.8 mg/g and 10.4 mg/g respectively. Presence of other co-ions in the medium doesn't affect the sorption process. Isothermal studies infer the adsorption follows Langmuir model and thermodynamic parameters concludes the endothermic and randomness of the adsorption. The bio-composites can be recycled and used upto three cycles. Field trial was conducted and the composites work well in such conditions.

A Perspective on Newly Emerging Proteolysis-Targeting Strategies in Antimicrobial Drug Discovery.

Targeted protein degradation is a new aspect in the field of drug discovery. Traditionally, developing an antibiotic includes tedious and expensive processes, such as drug screening, lead optimization, and formulation. Proteolysis-targeting chimeras (PROTACs) are new-generation drugs that use the proteolytic mechanism to selectively degrade and eliminate proteins involved in human diseases. The application of PROTACs is explored immensely in the field of cancer, and various PROTACs are in clinical trials. Thus, researchers have a profound interest in pursuing PROTAC technology as a new weapon to fight pathogenic viruses and bacteria. This review highlights the importance of antimicrobial PROTACs and other similar "PROTAC-like" techniques to degrade pathogenic target proteins (i.e., viral/bacterial proteins). These techniques can perform specific protein degradation of the pathogenic protein to avoid resistance caused by mutations or abnormal expression of the pathogenic protein. PROTAC-based antimicrobial therapeutics have the advantage of high specificity and the ability to degrade "undruggable" proteins, such as nonenzymatic and structural proteins.