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1.
Adv Healthc Mater ; 13(6): e2302790, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37909063

ABSTRACT

Augmentation of the activity of Food and Drug Administration-approved antibiotics by an adjuvant or antibiotic carrier is considered one of the promising strategies to fight against antibiotic-resistant bacteria. This study reports the development of sulfonium-cross-linked hyaluronic acid (HA)-based polymer (HA-SS-HA) as an inherent antimicrobial agent and antibiotic carrier. The HA-SS-HA polymer offers the potential for encapsulating various classes of antibiotics and accomplishing a stimuli-responsive release profile in the presence of hyaluronidase produced by bacterial cells within their extracellular environment. Systematic antibacterial studies reveal that the HA-SS-HA-encapsulated antibiotics (vancomycin, amoxicillin, and tetracycline) restore its activity against the antibiotic-resistant bacterial cells methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE), and Pseudomonas aeruginosa. The HA-SS-HA gel shows robust efficacy in eradicating the mature biofilm of Staphylococcus aureus (S. aureus). The membrane-disrupting activity reveals that HA-SS-HA can also counteract the antibiotic resistance mechanism of the bacterial cells. The in vivo studies reveal excellent wound-healing activity of HA-SS-HA in albino laboratory-bred (BALB/c) mice. The outcome of additional antibacterial studies reveals that antibiotics-encapsulated HA-SS-HA hydrogel can effectively combat Gram-negative, Gram-positive, and antibiotic-resistant bacterial strains. Therefore, revitalizing the activity of commercial antibiotics by HA-SS-HA can be considered a valuable and economically effective strategy to fight against antibiotic-resistant bacteria.


Subject(s)
Anti-Bacterial Agents , Methicillin-Resistant Staphylococcus aureus , United States , Animals , Mice , Anti-Bacterial Agents/pharmacology , Hyaluronic Acid/pharmacology , Hydrogels/pharmacology , Staphylococcus aureus , Bacteria , Drug Carriers/pharmacology , Polymers
2.
J Med Chem ; 66(16): 11078-11093, 2023 08 24.
Article in English | MEDLINE | ID: mdl-37466499

ABSTRACT

The increasing resistance of bacteria to commercially available antibiotics threatens patient safety in healthcare settings. Perturbation of ion homeostasis has emerged as a potential therapeutic strategy to fight against antibacterial resistance and other channelopathies. This study reports the development of 8-aminoquinoline (QN) derivatives and their transmembrane Zn2+ transport activities. Our findings showed that a potent QN-based Zn2+ transporter exhibits promising antibacterial properties against Gram-positive bacteria with reduced hemolytic activity and cytotoxicity to mammalian cells. Furthermore, this combination showed excellent in vivo efficacy against Staphylococcus aureus. Interestingly, this combination prevented bacterial resistance and restored susceptibility of gentamicin and methicillin-resistant S. aureus to commercially available ß-lactam and other antibiotics that had lost their activity against the drug-resistant bacterial strain. Our findings suggest that the transmembrane transport of Zn2+ by QN derivatives could be a promising strategy to combat bacterial infections and restore the activity of other antibiotics.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Quinolines , Staphylococcal Infections , Animals , Humans , Zinc , Ionophores/therapeutic use , Thiourea/pharmacology , Thiourea/therapeutic use , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Staphylococcal Infections/drug therapy , Quinolines/pharmacology , Quinolines/therapeutic use , Microbial Sensitivity Tests , Mammals
3.
Chemistry ; 29(15): e202203595, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36592116

ABSTRACT

Palladium is a key element in fuel cells, electronic industries, and organic catalysis. At the same time, chromium is essential in leather, electroplating, and metallurgical industries. However, their unpremeditated leakage into aquatic systems has caused human health and environmental apprehensions. Herein, we reported the development of an sp2 carbon-conjugated fluorescent covalent organic framework with a guanidine moiety (sp2 c-gCOF) that showed excellent thermal and chemical stability. The sp2 c-gCOF showed effective sensing, capture, and recovery/removal of Pd(II) and Cr(VI) ions, which could be due to the highly accessible pore walls decorated with guanidine moieties. The fluorescent sp2 c-gCOF showed higher selectivity for Pd(II) and Cr(VI) ions, with an ultra-low detection limit of 2.7 and 3.2 nM, respectively. The analysis of the adsorption properties with a pseudo-second-order kinetic model showed that sp2 c-gCOF could successfully and selectively remove both Pd(II) and Cr(VI) ions from aqueous solutions. The polymer also showed excellent capture efficacy even after seven consecutive adsorption-desorption cycles. Hence, this study reveals the potential of fluorescent sp2 c-gCOF for detecting, removing, and recovering valuable metals and hazardous ions from wastewater, which would be useful for economic benefit, environmental safety, human health, and sustainability. The post-synthetic modification of sp2 c-COF with suitable functionalities could also be useful for sensing and extracting other water pollutants and valuable materials from an aqueous system.

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