Biological evaluation, proposed molecular mechanism through docking and molecular dynamic simulation of derivatives of chitosan

Malekshah, Rahime Eshaghi; Shakeri, Farideh; Aallaei, Mohammadreza; Hemati, Maral; Khaleghian, Ali

doi:10.1016/j.ijbiomac.2020.10.252

Cited by 24 publications

(5 citation statements)

References 70 publications

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“…Another proposed mechanism involves the binding of amino groups on Chitosan with the negatively charged phosphate groups of DNA by electrostatic interactions, resulting in the inhibition of transcription [ 66 ]. Recent molecular docking studies of Chitosan–DNA interaction confirmed the ability of Chitosan to bind to the major groove of DNA [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against Pseudomonas aeruginosa

et al. 2021

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The co-occurrence of increasing rates of resistance to current antibiotics and the paucity of novel antibiotics pose major challenges for the treatment of bacterial infections. In this scenario, treatments targeting bacterial virulence have gained considerable interest as they are expected to exert a weaker selection for resistance than conventional antibiotics. In a previous study, we demonstrated that a low-molecular-weight quaternized chitosan derivative, named QAL, displays antibiofilm activity against the major pathogen Pseudomonas aeruginosa at subinhibitory concentrations. The aim of this study was to investigate whether QAL was able to inhibit the production of relevant virulence factors of P. aeruginosa. When tested in vitro at subinhibiting concentrations (0.31–0.62 mg/mL), QAL markedly reduced the production of pyocyanin, pyoverdin, proteases, and LasA, as well as inhibited the swarming motility of three out of four P. aeruginosa strains tested. Furthermore, quantitative reverse transcription PCR (qRT-PCR) analyses demonstrated that expression of lasI and rhlI, two QS-related genes, was highly downregulated in a representative P. aeruginosa strain. Confocal scanning laser microscopy analysis suggested that FITC-labelled QAL accumulates intracellularly following incubation with P. aeruginosa. In contrast, the reduced production of virulence factors was not evidenced when QAL was used as the main polymeric component of polyelectrolyte-based nanoparticles. Additionally, combination of sub-MIC concentrations of QAL and tobramycin significantly reduced biofilm formation of P. aeruginosa, likely due to a synergistic activity towards planktonic bacteria. Overall, the results obtained demonstrated an antivirulence activity of QAL, possibly due to polymer intracellular localization and QS-inhibition, and its ability to inhibit P. aeruginosa growth synergizing with tobramycin.

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Section: Discussionmentioning

confidence: 99%

Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against Pseudomonas aeruginosa

et al. 2021

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“…Although the mechanism of the antibacterial action of chitosan and its derivative is not yet certainly understood, three proposed mechanisms have been reported to explore this aspect 64 , 65 . The first mechanism which considered the most acceptable one for this study as it involves the electrostatic interaction between the positive charges of chitosan/or its derivative and the negative charges on the cell wall of bacteria, which incites leakage of intracellular ingredients (i.e., amino acids, proteins, glucose, and lactic dehydrogenase) because of disruption of the bacterial cell membrane.…”

Section: Resultsmentioning

confidence: 99%

Developing a new multi-featured chitosan-quinoline Schiff base with potent antibacterial, antioxidant, and antidiabetic activities: design and molecular modeling simulation

Abdel-Baky,

Omer,

El-Fakharany

et al. 2023

Sci Rep

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A new chitosan Schiff base was developed via the reaction of chitosan (CH) with 2-chloro-3-formyl-7-ethoxy quinoline (Q) derivative. The alteration in the chemical structure and morphology of CHQ derivative was confirmed by 1H NMR, FT-IR spectroscopy and SEM analysis. The antibacterial activity was considerably promoted with increasing quinoline concentration up to 1 M with maximal inhibition reached 96 and 77% against Staphylococcus haemolyticus and Escherichia coli, respectively. Additionally, CHQ derivative afforded higher ABTS·+ radical scavenging activity reached 59% compared to 13% for native chitosan, approving its acceptable antioxidant activity. Moreover, the developed CHQ derivative can stimulate the glucose uptake in HepG-2 and yeast cells, while better inhibition of α-amylase and α-glucosidase was accomplished with maximum values of 99.78 and 92.10%, respectively. Furthermore, the molecular docking simulation clarified the binding mode of CHQ derivative inside the active site of α-amylase and α-glucosidase, suggesting its potential use as diabetes mellitus drug. The DFT calculations indicated an improvement in the electronic properties of CHQ with a lower energy band gap reached 4.05eV compared to 5.94eV for CH. The cytotoxicity assay revealed the safety of CHQ towards normal HSF cells, hypothesizing its possible application as non-toxic antibacterial, antioxidant, and antidiabetic agent for biomedical applications.

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“…The first mechanism includes the electrostatic attraction between the positive charge amine groups (NH 3 + ) of chitosan and the negative charges on the cell wall of bacteria, which consequently which incites leakage of intracellular ingredients. The second mechanism concerned with the chelating capability of chitosan toward metal ions such as Ca 2+ , Mg 2+ , and Zn 2+ [50]. These metal ions are necessary for bacterial growth in addition to their role in the metabolic pathways such as spore formation in Gram-positive bacteria.…”

Section: Evaluation Of Antibacterial Activitymentioning

confidence: 99%

Novel Cytocompatible Chitosan Schiff Base Derivative as a Potent Antibacterial, Antidiabetic, and Anticancer Agent

et al. 2023

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This study intends to develop a novel bioactive chitosan Schiff base (CTS-SB) derivative via coupling of chitosan (CTS) with 4-((5, 5-dimethyl-3-oxocyclohex-1-en-1-yl) amino) benzene-sulfonamide. The alteration in the chemical structure of CTS-SB was verified using 1H NMR and FT-IR analysis, while the thermal and morphological properties were inspected by TGA and SEM characterization tools, respectively. Ion exchange capacity of the developed CTS-SB derivative recorded a maximal value of 12.1 meq/g compared to 10.1 meq/g for pristine CTS. In addition, antibacterial activity of CTS-SB derivative was greatly boosted against Escherichia coli (E coli) and Staphylococcus aureus (S. aureus) bacteria. Minimum inhibition concentration of CTS-SB derivative was perceived at 50 µg/mL, while the highest concentration (250 µg/mL) could inhibit the growth of S. aureus up to 91%. What’s more, enhanced antidiabetic activity by CTS-SB derivative, which displayed higher inhibitory values of α-amylase (57.9%) and α-glucosidase (63.9%), compared to those of pure CTS (49.8 and 53.4%), respectively Furthermore, cytotoxicity investigation on HepG-2 cell line revealed potential anticancer activity along with good safety margin against primary human skin fibroblasts (HSF cells) and decent cytocompatibility. Collectively, the gained results hypothesized that CTS-SB derivative could be effectively applied as a promising antibacterial, anticancer and antidiabetic agent for advanced biomedical applications.

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Biological evaluation, proposed molecular mechanism through docking and molecular dynamic simulation of derivatives of chitosan

Cited by 24 publications

References 70 publications

Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against Pseudomonas aeruginosa

Antivirulence Properties of a Low-Molecular-Weight Quaternized Chitosan Derivative against Pseudomonas aeruginosa

Developing a new multi-featured chitosan-quinoline Schiff base with potent antibacterial, antioxidant, and antidiabetic activities: design and molecular modeling simulation

Novel Cytocompatible Chitosan Schiff Base Derivative as a Potent Antibacterial, Antidiabetic, and Anticancer Agent

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