Successful synthesis of transmission systems containing fluoroquinolone framework compounds

13/10/2023

Dr. Le Nhat Thuy Giang and the research team of the Institute of Chemistry in collaboration with the research team of the Friendship University of Peoples (Russian Federation) have successfully synthesized a conduction system containing fluoroquinolone framework compound with potential applications in the field of biomedicine. This is the result of the project “Synthesis of several biodegradable compatible systems for fluoroquinolone transmission", code: QTRU01.12/20-21. The task was graded Excellent by the Acceptance Council of Vietnam Academy of Science and Technology.

Today, developing approaches to the rational use of drugs through delivering drugs to pharmacological targets is fundamental to the field of medicinal chemistry in order to significantly reduce side effects and undesirable effects, thereby enabling safe and effective use of drugs. One of the important directions to solve this problem is the development of transmission systems containing fluoroquinolone framework compounds using carriers such as copolymers of lactic acid and glycolic acid, liposomes, peptides and polysaccharides. Chitosan is a cationic polysaccharide that has unique properties including biocompatibility, biodegradability, no toxicity, and no immunity. Chitosan and its derivatives have been successfully used as nano substrates for the targeted delivery of various drugs. These advantages make chitosan an attractive and unique material for creating nanoscale substrates for delivering fluoroquinolones to action targets. Chitosan-based complexes in combination with ciprofloxacin have shown significantly higher antimicrobial efficacy than ciprofloxacin, where E. coli in vitro and in vivo antimicrobial activity is very high, and the chitosan-ciprofloxacin system has low overall toxicity. However, until now, there has not been much in-depth research on the chitosan-fluoroquinolone system, especially on the direction of creating polymer-fluoroquinolone or polymer-ligand bonds to bind to bacterial cells to improve the efficiency of conjugate systems.

The mission successfully synthesized chitosan-triazole derivatives by click reaction, then created chitosan-triazole conjugate systems with ciprofloxacin by amidization reaction using DCC/DMAP catalytic system. Chitosan-triazole-ciprofloxacin conjugate systems are comparable in antimicrobial capacity on Staphylococcus aureus and Escherichia coli strains to ciprofloxacin standards, and better than chitosan and chitosan-triazole derivatives. The chitosan-triazole-ciprofloxacin conjugate systems have been studied regarding the kinetics of ciprofloxacin release. In its normal form, ciprofloxacin did not separate from the conjugate systems for at least 80 hours of the test. For the nanoform, ciprofloxacin separated from NP-10 conjugates reached about 30-35% after 50 hours of testing, whereas ciprofloxacin was almost released from NP-11 conjugates after about 25 hours of testing. The results show that the chitosan-triazole-ciprofloxacin conjugate systems are biodegradable and can deliver ciprofloxacin to the target.

Pathways for the synthesis of chitosan-triazole-ciprofloxacin conjugate systems

The mission also investigated the successful synthesis of triazole-chitin derivatives and triazole-chitin nano derivatives. Triazole-chitin derivatives and nano triazole-chitin are both comparable in antimicrobial capabilities to ampicillin and gentamicin, which are much better than chitosan. At the same time triazole-chitin and nano triazole-chitin have no toxicity on NIH 3T3 normal cells. With good solubility in water, antimicrobial activity and low toxicity, chitosan-triazole, chitin-triazole derivatives and chitosan-triazole-ciprofloxacin conjugate systems and their nanoforms can be applied as potential antimicrobial agents.

In addition, the mission synthesized biocomposite nanocomposite films that can be used to protect food from bacteria and fungi from chitosan-based nanoparticles. The nanoparticles were synthesized from polyethylene glycol/methyl cellulose (PEG/MC), anthocyanidins, sodium acetate and crusts from chitosan/gallotannins. This chitosan-based nanocomposite film has the following properties: (i) odorless, non-toxic, advanced mechanical and barrier properties; (ii) high antimicrobial properties, antifungal, antioxidant and anti-UV activity; (iii) can indicate time-temperature.

Chitosan-based nanocomposite film

The research team published 02 works: "Water-soluble triazole chitin derivative and its based nanoparticles: Synthesis, characterization, catalytic and antibacterial properties" in the journal Carbohydrate Polymers (SCI, IF=10.7) and "Novel biopolymer-based nanocomposite food coatings that exhibit active and smart properties due to a single type of nanoparticles" in the journal Food Chemistry (SCI, IF = 9.2).

Translated by Phuong Ha
Link to Vietnamese version

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