A method for the synthesis of mixed-ligand gold glyconanoparticles with average particle size of 20–25 nm at widely variable ratio of the initial glycoligands on the basis of aldoses 6-mercaptohexanoyl hydrazones—condensation products of a series of natural aldoses (N-acetylamino-D-glucose, D-mannose, D-galactose, and L-fucose) with 6-mercaptohexanoic acid hydrazide—has been developed. It has been shown that the obtained gold glyconanoparticles exhibit low toxicity and are active against influenza A/Puerto Rico/8/34 (H1N1) virus at concentrations of 3 and 6 μg/mL.

Structure of previously unknown aldose 1,2-dithiolan-3-pentanoyl hydrazones—condensation products of a series of monosaccharides (L-fucose, L-rhamnose, D-mannose, D-galactose, N-acetylamino-D-glucose and N-acetylamino-D-mannose) with lipoic acid hydrazide was studied by spectral methods. It was shown that all the obtained compounds exist in DMSO-d₆ solution as a tautomeric mixture of open hydrazone and cyclic pyranose forms. The linear hydrazone form is represented by a set of Z′,E′-conformational isomers, differing in the arrangement of substituents relative to the C–N amide bond, in comparable amounts. On the basis of the indicated aldose 1,2-dithiolan-3-pentanoyl hydrazones, a method for the synthesis of gold glyconanoparticles with an average particle diameter of 23–28 nm and a low value of the polydispersity index has been developed. It was shown that individual aldose 1,2-dithiolan-3-pentanoyl hydrazones have a significant radioprotective effect, and glyconanoparticles based on them increase the effectiveness of radiation therapy for Ehrlich carcinoma.

INTRODUCTION: Use of metal nanoparticles is a promising trend in oncotherapy. AIM: To evaluate cytotoxicity of gold nanoparticles (GNPs) modified with fucose, lactose and galactose residues, on Caco-2 cells. MATERIALS AND METHODS: Cells were cultured to a monolayer with GHPs in concentrations of 10 g/ml600 g/ml for particles with fucose, 10 g/ml900 g/ml for particles with lactose and 10 g/ml550 g/ml for particles with galactose. As non-tumor cells, Caco-2 cells were used after differentiation into small-intestine enterocytes (incubation time 21 days). The cytotoxicity of GNPs was evaluated in MTT-test after incubation with cells for 2 hours, 8 hours and 24 hours. A comparison drug was fluorouracil in concentrations of 50 g/ml2000 g/ml. The half-maximal inhibitory concentration (IC50) was calculated in GraphPad Prism 8.4.3 program. RESULTS: IC50 for GNPs with fucose for tumor cells was 582 29 and 336 36 g/ml after incubation for 2 hours and 8 hours, respectively; for GNPs with lactose 769 50 and 515 45 g/ml, for GNPs with galactose 467 299 and 299 28 g/ml. For differentiated cells, IC50 for all types of GNPs was higher than for tumor cells after incubation for 2 and 8 hours: for particles with fucose 530 3 and 410 15 g/ml; for particles with lactose 831 7 and 639 14 g/ml; for particles with galactose 511 21 (p = 0.018) and 376 36 g/ml, respectively. After 24-hour incubation of Caco-2 cells with fucose, IC50 did not differ for tumor and differentiated varieties. For other GNPs, IC50 for tumor cells was higher than for differentiated cells. Fluorouracil showed cytotoxicity for tumor cells with IC50 2108 19 and 1764 193 g/ml after 2 hours and 8 hours of incubation, respectively. For differentiated cells, IC50 of fluorouracil was 1694 102 g/ml after 2-hour incubation and 1694 102 g/ml after 8-hour incubation. There were no differences between IC50 of fluorouracil for differentiated and tumor cells with equal incubation time. CONCLUSION: GNPs with fucose, lactose and galactose have a cytotoxic effect on human colon adenocarcinoma cells and in the activity are superior to fluorouracil.

The two-step method for the synthesis of previously unknown 1-hydroxy-2,3-dihydropyrazolo[1,2-c]­benzo-1,3,4-thiadiazepin-11(5H)-one has been developed based on 2-mercaptobenzoic acid hydrazide and commercially available formaldehyde and acrolein. The synthesized compound, which has a targeted antitumor effect, is a promising bioactive co-ligand for obtaining gold glyco-nanoparticles for biomedical purposes.

The reaction of 4-hydroxy-1-phenyl-6-methyltetrahydropyrimidine-2(1H)-thione with 6-sulfanylhexanoic and lipoic (thioctic) acid hydrazides forms 4-[ω-(sulfanylacyl)hydrazino]tetrahydropyrimidine-2(1H)-thiones in yields of 60–75%. The products are promising сo-ligands for the preparation of glyco-gold nanoparticles for biomedical purposes.

The reaction of 1,4-dithiane-2,5-diol with 2-sulfanylbenzohydrazide afforded 55% of previously unknown 2-(sulfanylmethyl)-1,3,4-benzothiadiazepin-5(2H)-one whose structure was confirmed by ¹H and ¹³C NMR spectra.