A three-step method for obtaining pyrrolo[1,2-a]pyrazine-4,7-dicarboxylates was presented. The method involves the N-alkylation of 5-formylpyrrole-3-carboxylates with bromoacetate, followed by the aminoalkenylation of the N-alkoxycarbonylmethyl group using dimethylformamide di-tert-butyl acetal, and further annulation of the pyrazine ring in the presence of ammonium acetate. Procedures for selective hydrolysis, halogenation, arylation, and alkynylation of the synthesized dicarboxylates were described. The in silico evaluation of the potential bioactivity of the synthesized dicarboxylates 4a–f, dicarboxylic acids 7a–c,e, halogenated dicarboxylates 8f–j, and dicarboxylic acids 10a–e was carried out. As seen from the screening of antimicrobial activity, the synthesized compounds 7a–e, 8c,f–j, 10a–e exhibit inhibitory and bactericidal activity against several bacteria and fungi. The highest activity against Klebsiella pneumonia, Staphylococcus aureus, and Bacillus subtilis has been established for the compound 8f with a MIC of 15.625 µg/mL, and the highest antifungal activity against Candida albicans was found for the compounds 8f, 8g, and 8i (МІС=15.625 µg/mL). The molecular docking data show that the compound 8i has the highest affinity to the ThiM Klebsiella pneumoniae kinase, and compounds 8i, 8j are noted for their highest affinity to the DNA gyrase from Staphylococcus aureus.

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.

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.

A series of new 4-(1,3,4-thiadiazol-2-yl)-containing polysubstituted pyrroles 3 a-k has been synthesized by a preparative convenient method from ethyl 5-chloro-4-formyl-1H-pyrrole-3-carboxylates 1 a-e, which were selectively transformed into the corresponding polysubstituted pyrrole-4-carboxylic acids 2 а-е using sodium hypochlorite as an oxidizer. Further, they were transformed into the target compounds with a high yield using the cyclocondensation with N-mono- or N,N-disubstituted thiosemicarbazides in the boiling phosphorus trichloroxide. As seen from the screening of antimicrobial activity, the synthesized compounds exhibit the inhibiting and bactericide activity against some bacteria and fungi. The highest activity has been established for the compounds 3 a, c, e-h, j against the strain Klebsiella pneumoniae (МІС=31.25 µg/mL). The calculated HOMO energy level proves that the compound 3 с is the most reactive ligand for the interaction with a protein receptor. The molecular docking data show that the compound 3 h has the highest affinity to the ThiM Klebsiella pneumoniae kinase.