Combined antimicrobial agents based on self-assembled PAMAM-calix-dendrimers/lysozyme nanoparticles: Design, antibacterial properties and cytotoxicity

Padnya, Pavel L.; Mostovaya, O. A.; Ovchinnikov, D. V.; Shiabiev, Igor; Pysin, Dmitry; Akhmedov, A. A.; Mukhametzyanov, Timur A.; Lyubina, Anna P.; Voloshina, Alexandra D.; Петров, К. А.; Стойков, И. И.

doi:10.1016/j.molliq.2023.122838

Cited by 8 publications

(1 citation statement)

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“…A recent review by Prof. Duval's group [59] detailed the benefits of the (thia)calixarene platforms, e.g., the use of a multivalent approach to obtain the target compounds, the possibility of easy functionalization with positively charged fragments (e.g., ammonium, guanidinium, and imidazolium), and the spatial organization of these fragments by obtaining different stereoisomeric forms, i.e., cone, partial cone, and 1,3-altenate. Previously, our research group has shown that thiacalix [4]arene derivatives containing eight primary terminal amino groups and their complexes with lysozyme have antibacterial properties [60]. However, the synthetic approaches proposed earlier in the literature do not allow for the possibility of "fine-tuning" the structure of the target compounds by the introduction of different functional groups.…”

Section: Introductionmentioning

confidence: 99%

Towards Antibacterial Agents: Synthesis and Biological Activity of Multivalent Amide Derivatives of Thiacalix[4]arene with Hydroxyl and Amine Groups

Shiabiev,

Pysin,

Akhmedov

et al. 2023

Pharmaceutics

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Antimicrobial resistance to modern antibiotics stimulates the search for new ways to synthesize and modify antimicrobial drugs. The development of synthetic approaches that can easily change different fragments of the molecule is a promising solution to this problem. In this work, a synthetic approach was developed to obtain multivalent thiacalix[4]arene derivatives containing different number of amine and hydroxyl groups. A series of macrocyclic compounds in cone, partial cone, and 1,3-alternate stereoisomeric forms containing -NHCH2CH2R (R = NH2, N(CH3)2, and OH) and -N(CH2CH2OH)2 terminal fragments, and their model non-macrocyclic analogues were obtained. The antibacterial activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, and Enterococcus faecalis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains and cytotoxicity of the obtained compounds were studied. Structure–activity relationships were established: (1) the macrocyclic compounds had high antibacterial activity, while the monomeric compounds had low activity; (2) the compounds in cone and partial cone conformations had better antibacterial activity compared to the compounds in 1,3-alternate stereoisomeric form; (3) the macrocyclic compounds containing -NHCH2CH2N(CH3)2 terminal fragments had the highest antibacterial activity; (4) introduction of additional terminal hydroxyl groups led to a significant decrease in antibacterial activity; (5) the compounds in partial cone conformation had significant bactericidal activity against all studied cell strains; the best selectivity was observed for the compounds in cone conformation. The mechanism of antibacterial activity of lead compounds with terminal fragments -NHCH2CH2N(CH3)2 was proved using model negatively charged POPG vesicles, i.e., the addition of these compounds led to an increase in the size and zeta potential of the vesicles. The obtained results open up the possibility of using the synthesized macrocyclic compounds as promising antibacterial agents.

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Section: Introductionmentioning

confidence: 99%