Synthesis and structure-activity-toxicity relationships of DABCO-containing ammonium amphiphiles based on natural isatin scaffold

• Type: Article in International Scientific Journal
• Date: 2022

Authors

Pashirova, TN (Author) Other; Shaihutdinova, ZM (Author) Other; Vandyukov, AE (Author) Other; Lyubina, AP (Author) Other; Amerhanova, SK (Author) Other; Voloshina, AD (Author) Other; Samorodov, AV (Author) Other; Souto, EB (Author) FFUP; Mironov, VF (Author) Other; Bogdanov, AV (Author) Other

Journal

Title: Journal of Molecular Liquids

Vol. 365

ISSN: 0167-7322

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 0 Citations

Scopus

Other information

Authenticus ID: P-00X-4YV

DOI: 10.1016/j.molliq.2022.120217

Abstract (EN): This work deals with the creation of new multifunctional quaternary ammonium compounds (QACs) on natural isatin scaffold as a new generation of antimicrobial agents. 1-R-isatin-3-acylhydrazones containing quaternized DABCO moieties (Dabco-Is-n) with varying hydrophobicity (R = CnH2n+1, where n = 10, 12, 14, 16, 18) were synthesized. The idea was to combine two bactericidal fragments, presumably with different mechanisms of action, in the structure of self-assembling quaternary ammonium compounds. The self-assembly behavior, solubility properties toward hydrophobic dye Sudan I, antimicrobial activity against gram-positive and gram-negative bacteria, fungi, hemolytic activity, cell toxicity (MTT-test) and in vitro anticoagulant and anti-aggregation activities were investigated. Established by tensiometry, conductometry, dynamic light scattering and UV-spectrophotometry, the value of Dabco-Is-n critical micelle concentration is 10 times lower than for Dabco-n surfactants. That is, Dabco-Is-n self -assemblies are responsible factor for the manifestation of antimicrobial activity. Dabco-Is-12 was found to be largely blood biocompatible with low toxicity and low hemolysis (IC50 and HC(50 )are >= 100 lM, neg-ligible coagulation) and with high biological activity against methicillin-resistant strains of S. aureus MRSA-1 and MRSA-2 (MIC = 3.5 and 7.0 mu M, respectively) and high solubilization capacity toward hydrophobic dye (Sudan I). Moreover, it forms hydrogen-bonds with drugs (niclosamide and piperine) and displays a good selectivity index toward fungi Candida albicans ATCC 10231. Such new nontoxic Dabco-Is-n biocides with antibacterial and antifungal effects have a good potential for medical applications.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11