Nitroaromatic compounds (ArNO₂) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction performed by various flavoenzymes and/or their physiological redox partners, metalloproteins. The pivotal and still incompletely resolved questions in this area are the identification and characterization of the specific enzymes that are involved in the bioreduction of ArNO₂ and the establishment of their contribution to cytotoxic/therapeutic action of nitroaromatics. This review addresses the following topics: (i) the intrinsic redox properties of ArNO₂, in particular, the energetics of their single- and two-electron reduction in aqueous medium; (ii) the mechanisms and structure-activity relationships of reduction in ArNO₂ by flavoenzymes of different groups, dehydrogenases-electrontransferases (NADPH:cytochrome P-450 reductase, ferredoxin:NADP(H) oxidoreductase and their analogs), mammalian NAD(P)H:quinone oxidoreductase, bacterial nitroreductases, and disulfide reductases of different origin (glutathione, trypanothione, and thioredoxin reductases, lipoamide dehydrogenase), and (iii) the relationships between the enzymatic reactivity of compounds and their activity in mammalian cells, bacteria, and parasites.

Triazole derivatives constitute an important group of heterocyclic compounds have have been the subject of extensive study in the recent past. These compounds have shown a wide range of biological and pharmacological activities. In this work, new fused tricyclic 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]-benzodiazepines have been synthesized by the thermal cyclization of N'-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-3-nitrobenzohydrazides. After screening ethanol, toluene and 1-butanol as solvents, butanol-1 was found to be the best choice for the cyclization reaction in order to obtain the highest yields of tricyclic derivatives. The chemical structures of the synthesized compounds were elucidated by the analysis of their IR, ¹H- and ¹³C-NMR spectral data. For tentative rationalization of the reaction processes, the global and local reactivity indices of certain compounds, taking part in the reaction pathway, were assessed by means of quantum mechanical calculations using the conceptual density functional theory (DFT) approach. This work could be useful for the synthesis of new heterocyclic compounds bearing a fused triazole ring.

Oxidation of 1,3,4,5-tetrahydro-2H-1,5-benzodiazepine oximes catalysed by horseradish peroxidase (HRP) and recombinant Coprinus cinereus peroxidase (rCiP) was studied spectrophotometrically. The reaction rate dependences on the substrate and hydrogen peroxide concentrations were investigated; the values of apparent KM and Vmax, catalytic, oxidation and reduction constants (kcat, kox and kred, respectively) were calculated. The reactivity constants for the reactions catalysed by rCiP were higher than those for the HRP. Since oximes can have different structures depending on pH, the influence of pH on the rate of oxidation of compounds was studied. The dependences of the oxidation rate of the investigated oximes on the pH of the buffer solution were determined, and the pKa values of the amino acids of peroxidases responsible for the rate of catalysis were obtained. The HRP activity dependence on pH has a classical bell-shaped character, while rCiP dependence has a complex character.

The modification of heterocyclic systems remains one of the most promising areas in heterocyclic chemistry. Benzodiazepines (BZDs), representing a diverse class of heterocyclic molecules, have piqued interest due to their use as anticonvulsant/anti-inflammatory/analgesic/sedative/anti-depressive/hypnotic medications, as well as anti-inflammatory/anti-HIV drugs. Phosphorus heterocycle molecules fused with rings of different sizes and bearing various heteroatoms have also been attracting much interest. Phosphoramidate class compounds with an amino group linked directly to the phosphorus atom have gained considerable attention due to their wide range of biological activity and agricultural application. To date, however, only non-condensed monocyclic 1,3,5,2-oxodiazaphosphol-2-oxides have been described.Herein, we report the synthesis of previously undescribed 4H-[1,3,5,2]oxadiazophospho[3,4-a][1,5]benzodiazepine-1-amino-1-oxides, comprising benzodiazepine and a fused five-member oxodiazophospholo cycle with four heteroatoms in the “a” position, which was made possible by phosphorylation of 1,3,4,5-tetrahydro-2H-1,5-benzodiazepin oximes with an equimolar amount of dimethylaminophosphoric acid dichloride. The chemical structures of the compounds were confirmed by IR, ¹H, ¹³C, and ³¹P NMR spectral analysis. A series of simulations were conducted by employing the semi-empirical, tight-binding computational technique GFN2-xTB to reveal the likely pathways leading to their formation. The synthesised compounds obeyed Lipinski’s rule, implying a good bioavailability, and assessment of their projected drug-like abilities revealed that they may have a strong anti-neoplastic activity and, to a lesser extent, may act as both substrates and inducers of cytochrome P-450 (CYP) super-family enzymes.