Antioxidant activity of a series of previously described 5-amino-N-(iododi(per)fluoroalkyl)-1H-1,2,3-triazole-4-carboxamides 3a-r, their synthetic precursors 5-amino-N-allyl-1,2,3-triazole-4-carboxamides 1a-g, and their deamination products N-(3-di(per)fluoroalkyl-2-iodo-n-propyl)-1,2,3-triazole-4-carboxamides 4a-e was investigated in vitro using DPPH test and ascorbic acid as a standard reference. It was established that compounds 3a-r inhibit DPPH free radicals in moderate to high values (50.9–97.6%). The effect of substituents in the position 1 of the 1,2,3-triazole nucleus, fluoroalkyl groups and amino groups on the level of antioxidant activity was studied in detail. Reactivity and electrostatic surface potential were evaluated for the most active carboxamides 3a,g,r using the DFT method, and molecular docking was studied in the NADPH oxidase protein model.

Continuing the search for new antimicrobial agents with antibiofilm activity, bis-quaternary ammonium compounds based on natural (3,5-dibromo-4-hydroxyphenyl)acetic acid derivatives were synthesized. Antibacterial and antibiofilm activity of ammonium salts was evaluated in vitro against S. aureus, E. coli, and P. aeruginosa, including antibiotic-resistant strains. Bis-quaternary ammonium salts 1, 5, and 6 showed antibacterial activity with MIC values ranging from 25.0 to 200.0 μg/mL. Notably, these compounds demonstrated a high level of antibiofilm activity. Ammonium salts 1 and 6 reduced biofilm formation against S. aureus ATCC 25923, P. aeruginosa PA01, E. coli ATCC 25922, and antibiotic-resistant P. aeruginosa by 92 - 97% at a concentration of 100.0 μg/mL. In addition, compounds 1 and 6 inhibited the biofilm formation of antibiotic-resistant E. coli isolate by 60% and 63%, respectively.

In the present work, we report an efficient synthesis and antioxidant activity evaluation of some 4-arylimino-thiazolidin-2-ones. The structures of target substances were confirmed through ¹H and ¹³C NMR spectroscopy, mass spectrometry and elemental analysis. The antioxidant activity of the synthesized compounds was measured in vitro by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. Notably, antioxidant activity was identified for the first time among 4-arylimino-thiazolidin-2-ones.

A preparatively convenient method is proposed for the synthesis of new 1-oxo-3,4-dihydro-1H-pyrrolo[2,1-с][1,4]oxazine-8- 4a-e and 4-oxo-4H-pyrrolo[2,1-c][1,4]benzoxazine-3-carboxylic acids 5a-f that is based on the interaction of methyl (2-oxomorpholin-3-ylidene)ethanoates 1a-e and methyl (2-oxo-2H-1,4-benzoxazine-3(4H)-ylidene)ethanoates 2a-f with 2-bromo-1,1-diethoxyethane. Obtained acids were transformed into the corresponding tert-butyl carbamates 6a-e, 7a-f and N-alkyl(aryl)carboxamides 11a-i, 12a-d. By treating tert-butyl carbamates 6a-e, 7a-f with hydrogen chloride, 8-amino-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazin-1-ones 8a-e and 3-amino-4H-pyrrolo[2,1-c][1,4]benzoxazin-4-ones 9a-f were obtained. By acylation of amines 8a-e, 9a-f with acetic anhydride, benzoyl chloride, methanesulfonyl chloride, and p-toluenesulfonyl chloride, corresponding N-acetamides 13a,b, 14, N-benzamides 15, 16, N-methanesulfonamides 17, 18, and N-p-toluenesulfonamides 19, 20 were synthesized. In total, 30 new derivatives of 1-oxo-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazinones and 27 new 4-oxo-4H-pyrrolo[2,1-c][1,4]benzoxazinones were obtained.

A number of 3-aryl-5,6-dihydroimidazo[2,1-b][1,3]thiazoles were synthesized by cyclocondensation of imidazolidine-2-thione with phenacyl bromides, and their antimicrobial and antioxidant activity was evaluated. Bioscreening confirmed the moderate antibacterial activity against the reference strains of bacteria Staphylococcus aureus, Escherichia coli and Proteus vulgaris and excellent antifungal activity against Candida albicans. It was found that 3-(4-chlorophenyl)-5,6-dihydroimidazo[2,1-b]thiazole 4h (MIC = 15.625 μg/ml) has twice the antifungal effect compared to the control drug Furacilin. The study of the antioxidant activity of the synthesized compounds proved their ability to inhibit 60–97% of DPPH radicals. The best antiradical effect was found for 4-(5,6-dihydroimidazo[2,1-b]thiazol-3-yl)phenol 4e (I = 97%). A probable mechanism of its action was proposed involving the formation of a radical cation by the SET process. For the most active antioxidants 4e-g, reactivity and electrostatic surface potential were evaluated using the DFT method, and molecular docking was studied on the human peroxiredoxin 5 protein model.

By the reaction of substituted benzaldehydes and indol-3-carbaldehydes (2E)-2-cyano-N-[5-(R-benzyl)-1,3-thiazol-2-yl]-3-(R1-phenyl)prop-2-enamides 3-(1-R¹-1H-indol-3-yl)-2-cyano-N-(5-(R-benzyl)-1,3-thiazol-2-yl)prop-2-enamides were synthesised. The antitumor activity of prepared compounds were investigated. 3-(1-Benzyl-¹H-indol-3-yl)-2-cyano-N-(5-(2-chlorobenzyl)-1,3-thiazol-2-yl)prop-2-enamide (7b) has been identified as hit compound with values of MG-MID GI50 = 3.903 µM, TGI = 29.10 µM, LC50 = 57.54 µM.

Fourteen novel 4-(5-amino-4-cyano-1,3-oxazol-2-yl)benzenesulfonamides have been designed, synthesized, and characterized by spectroscopy and spectrometry methods. They have also been investigated on the NCI-60 cancer cell lines. The most activity compounds, 2, 3, and 9, in concentration 10 µM demonstrated mean GI50 values of 77, 70, and 68%, respectively, against the tumor cells. The best activity compound 2 showed the following GI50 values: non-small cell lung cancer (HOP-92) - 4.56 µM, breast cancer (MDA-MB-468) - 21.0 µM, melanoma (SK-MEL-5) - 30.3 µM. Besides, this compound indicates low toxicity with TGI and LC50 values >100 µM against all cancer cell lines. The COMPARE analysis (NCI) of compound 2 showed a very high correlation (r=0.91) with Tamoxifen as a selective estrogen receptors modulator. Molecular docking studies of ligand 2 demonstrated the complexation with estrogen receptors as a possible antitumor mechanism. The ADMET analysis of compound 2 indicates an optimistic prediction as an antitumor agent.

This short communication reports about new 5-amino-4-(1H-tetrazol-5-yl)-1,3-oxazoles which were synthesized by [3+2] cycloaddition of 2-R-5-amino-1,3-oxazole-4-carbonitriles and trimethylsilyl azide with dibutyltin oxide present. The reaction conditions provided high yields of the products, and were tolerant to some active functional fragments in the oxazole substituents (amino, amido, and hydroxy group). In the case of 2-((4-cyano-2-phenyloxazol-5-yl)amino)-N-methylacetamide the by-product (N-((1-(2-(methylamino)-2-oxoethyl)-1H-tetrazol-5-yl)(1H-tetrazol-5-yl)methyl)-benzamide) was formed together with the expected tetrazolyloxazole.

It has been reported that the halogen dance reaction can be used to synthesize polyfunctionalized 1,3-thiazoles. The transformation into target products was carried out by lithiation of 2-bromo-5-(1,3-dioxolan-2-yl)-1,3-thiazole with lithium diisopropylamide (LDA) followed by treatment with various electrophiles. The obtained compounds were then successfully applied to prepare novel 4,5-difunctional thiazole derivatives.

Triazolo[3,4-b]thiadiazoles are a class of heterocyclic compounds, which have attracted great interest in medicinal chemistry owing to their wide range of pharmacological activities. A number of triazoles fused to thiadiazoles are incorporated into a wide variety of therapeutically important compounds possessing a broad spectrum of biological activities. Considering such a significant pharmacological potential, as well as wide synthetic possibilities triazolo-thiadiazoles have received considerable attention from scientific community and are extensively used for construction of prospective drug-likes molecules. In this review, we summarized the literature data about the main synthetic approaches for obtaining condensed heterocyclic compounds based on triazolo[3,4-b][1,3,4]thiadiazole scaffold as promising objects for modern bioorganic and medicinal chemistry.