Synthesis and characterization of pyridoxine, nicotine and nicotinamide salts of dithiophosphoric acids as antibacterial agents against resistant wound infection

Novel cationic amphiphiles of the 3-alkyl-1-(4methoxyphenyl)-1H-imidazol-3-ium bromide series bearing methoxyphenyl fragments (MPI-n) have been synthesized. Their aggregation properties in aqueous solutions, solubilization capacity, and hemolytic and antimicrobial activities have been investigated by a number of physicochemical methods. Using tensiometry, conductometry, and fluorescence spectroscopy, it was shown that the MPI-n have lower CMCs than their nonfunctionalized counterparts. The unusual alkyl-chain-length-dependent morphology of aggregates is testified for this homological series. Amphiphiles with 12, 14, and 16 alkyl tails are characterized by the formation of micellar aggregates, while a surfactant with a decyl tail is characterized by the formation of larger aggregates with lower surface curvature. The MPI-10 aggregate morphology was rationalized in terms of the packing parameter consideration and was supported by size measurements and the fluorescence probe techniques, which showed that vesicle-like aggregates in closepacking mode probably occur. MPI-n aggregates have exhibited a high solubilization capacity toward hydrophobic azo dye Orange OT. Importantly, amphiphiles studied showed (i) high bacteriostatic activity at the level of ciprofloxacin; (ii) high bactericidal action against all Gram-positive bacteria, including methicillin-resistant strains; (iii) bactericidal properties against Gram-negative bacteria; and (iv) low hemolytic activity.

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“…A detailed description of the method is given in an earlier work. 7,45,46 2.11. Hemolytic Activity of MPI-n Amphiphiles.…”

Section: Methodsmentioning

confidence: 97%

Cationic Imidazolium Amphiphiles Bearing a Methoxyphenyl Fragment: Synthesis, Self-Assembly Behavior, and Antimicrobial Activity

et al. 2022

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“…О,О-di-(-)-menthyldithiophosphoric acid 3 was obtained by the method [25]. The syntheses of (S)-(-)-nicotinic, pyridoxinic and 8S,9R-quinine salts of O,O-di-(-)dimenthyldithiophosphoric acid 9-11 were carried out according to the methods presented in articles [21] and [26].…”

Section: Methodsmentioning

confidence: 99%

“…Our research group curries out systematic research on the creation of biologically active drugs based on dithiophosphoric acids and their salts using nitrogenous organic compounds [21][22][23][24], many of these acids were obtained from monoterpene alcohols. We assumed that dithiophosphoric acids obtained from enantiomerically pure menthols and their salts can be of interest for studying nematicidal activity.…”

Section: Introductionmentioning

confidence: 99%

Nematicidal activity of menthol and its dithiophosphoric derivatives

et al. 2021

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The effects of (–)-(1R,2S,5R)-menthol and its dithiophosphoric derivatives - O,O-di-(–)-menthyldithiophosphoric acid, its sodium, 8S,9R-quinine, (S)-(–)-nicotinic and pyridoxonium salts on the organism of the free-living soil nematode Caenorhabditis elegans were investigated. (–)-(1R,2S,5R)-menthol had no toxic effect on nematodes. O,O-di-(–)-menthyldithiophosphoric acid and its sodium salt caused dose-dependent death of nematodes. The toxic effect of these substances on the C. elegans organism developed with a lag-phase and reached its maximum value after 24 hours at concentrations of O,O-di-(–)-menthyldithiophosphoric acid and its sodium salt of 500 and 400 μg/mL, respectively. The LC50 values were 191.5 μg/mL for O,O-di-(–)-menthyldithiophosphoric acid, and 181.6 μg/mL for its sodium salt. 8S,9R-quinine, (S)-(–)-nicotinium and pyridoxonium salts of O,O-di-(–)-menthyldithiophosphoric acid were less toxic against C. elegans, causing 89.5–98.5% death of nematodes upon 24 hour exposure at a concentration of 2000 μg/mL. The study of the antihelmintic properties of (–)-(1R,2S,5R)-menthyl dithiophosphoric derivatives is promising for the creation of drugs both for the treatment of helminthiasis in domestic animals and humans, and as well as nematicides to control phytonematodes parasitizing in plants.

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“…We have shown that dithiophosphoric acid (DTP) with O,O-diorganyl groups can protonate nitrogen-containing biomolecules with the participation of the acidic thiol group of DTP. The reaction produces ammonium salts between biomolecule (cation) and DTP (anion) with new properties and bioactivity over the constituents [ 23 , 24 ]. The potential of the DTP modifier in the regulation of biospecific properties of GSH and other peptide molecules is poorly known.…”

Section: Introductionmentioning

confidence: 99%

Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione

et al. 2021

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Phosphorus species are potent modulators of physicochemical and bioactive properties of peptide compounds. O,O-diorganyl dithiophoshoric acids (DTP) form bioactive salts with nitrogen-containing biomolecules; however, their potential as a peptide modifier is poorly known. We synthesized amphiphilic ammonium salts of O,O-dimenthyl DTP with glutathione, a vital tripeptide with antioxidant, protective and regulatory functions. DTP moiety imparted radical scavenging activity to oxidized glutathione (GSSG), modulated the activity of reduced glutathione (GSH) and profoundly improved adsorption and electrooxidation of both glutathione salts on graphene oxide modified electrode. According to NMR spectroscopy and GC–MS, the dithiophosphates persisted against immediate dissociation in an aqueous solution accompanied by hydrolysis of DTP moiety into phosphoric acid, menthol and hydrogen sulfide as well as in situ thiol-disulfide conversions in peptide moieties due to the oxidation of GSH and reduction of GSSG. The thiol content available in dissolved GSH dithiophosphate was more stable during air oxidation compared with free GSH. GSH and the dithiophosphates, unlike DTP, caused a thiol-dependent reduction of MTS tetrazolium salt. The results for the first time suggest O,O-dimenthyl DTP as a redox modifier for glutathione, which releases hydrogen sulfide and induces biorelevant redox conversions of thiol/disulfide groups.

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Synthesis and characterization of pyridoxine, nicotine and nicotinamide salts of dithiophosphoric acids as antibacterial agents against resistant wound infection

Cited by 38 publications

References 47 publications

Cationic Imidazolium Amphiphiles Bearing a Methoxyphenyl Fragment: Synthesis, Self-Assembly Behavior, and Antimicrobial Activity

Cationic Imidazolium Amphiphiles Bearing a Methoxyphenyl Fragment: Synthesis, Self-Assembly Behavior, and Antimicrobial Activity

Nematicidal activity of menthol and its dithiophosphoric derivatives

Dithiophosphate-Induced Redox Conversions of Reduced and Oxidized Glutathione

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