![]() The antimicrobial potentials of triazenes were determined according to their minimum inhibitory concentrations (MICs) these compounds were active against gram-positive and gram-negative bacteria, with low MIC values. The antimicrobial and antifungal activities of the compounds were tested by evaluating the sensitivity of bacteria (American Type Culture Collection, ATCC) and clinical isolates to their solutions using standardized microbiological assays, cytotoxicity evaluation, and ecotoxicity tests. This study describes the synthesis, molecular and crystalline structure, biological activity evaluation, and antifungal and antimicrobial potentials of 1,3-bis(X-methoxy-Y-nitrophenyl)triazenes. Triazenes are versatile and belong to a group of alkylating agents with interesting physicochemical properties and proven biological activities. In the present study, novel, 1,3-diaryltriazene-derived triazene compounds were synthesized and tested. Thus, transformation of aminoaromatic and aminoheterocyclic energetic materials into triazenes is a convenient method for enhancement of their detonation properties. Applying the same quantum-chemical methods for structural building blocks (constituents of triazenes) we have found that diazoamination always increases detonation performance (2-15% for detonation velocity and 0-32% for pressure). As a result, we have obtain good regression coefficients, R² = 0.91 (for dc) and R² = 0.96 (for ΔHf). To ensure that input parameters, namely, crystal density (dc) and enthalpy of formation (ΔHf) are correct, we have benchmarked a number of experimentally known triazenes as well as other structurally similar compounds. Then, top ten structures were calculated using quantum-chemical methods to obtain more accurate estimates of their detonation properties, which were calculated using the Kamlet-Jacobs equations. For this purpose, we selected 17 aminoaromatic and aminoheterocyclic energetic materials, both widely known and newly synthesized, and ranked all possible triazenes derived from them according to our recently developed compositional criterion evaluation algorithm. In this paper, we report a theoretical study of the change in detonation efficiency of energetic amines undergone diazoamination reaction. Our data suggest that 4-nitro-substituted 1,3-diaryltriazenes are a new class of anticancer molecules which preferentially target malignant cells and may serve as potential antitumor agents. Instead, 8b induces reactive oxygen species that could provoke endoplasmic reticulum (ER(a)) stress finally leading to apoptosis. DNA binding analysis suggests that neither 8b nor its non-acylated derivative 8a bind into the minor groove of DNA. Notably, its antiproliferative activity is significantly higher against tumor cells than against normal cells. Selected 3-acetyl-1,3-bis(2-chloro-4-nitrophenyl)-1-triazene (8b) is highly cytotoxic against different tumor cell lines, including cisplatin-resistant laryngeal carcinoma cells. The results of LC-MS/MS analysis showed that N-acyltriazenes can be considered as prodrugs of non-acylated triazenes. In order to increase the solubility of the modified compounds, we introduced various acyl groups to their triazene nitrogen. Structure-activity relationship analysis reveals that 1,3-diaryltriazenes can be modified from inactive to highly cytotoxic compounds by the introduction of two nitro groups at the para positions of benzene rings and two additional electron-withdrawing groups (bromo, chloro, trifluoromethyl or fluoro substituents) at their ortho position. We describe the synthesis and biological activity of a new class of 1,3-diaryltriazenes, namely 4-nitro-substituted 1,3-diaryltriazenes.
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