Novel Hybrid Compounds Containing Benzofuroxan and Aminothiazole Scaffolds: Synthesis and Evaluation of Their Anticancer Activity

A series of novel hybrid compounds containing benzofuroxan and 2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Tamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.     

Design,Synthesis and Antifungal/Nematicidal Activity of Novel 1,2,4-Oxadiazole Derivatives Containing Amide Fragments

Plant diseases that are caused by fungi and nematodes have become increasingly serious in recent years. However, there are few pesticide chemicals that can be used for the joint control of fungi and nematodes on the market. To solve this problem, a series of novel 1,2,4-oxadiazole derivatives containing amide fragments were designed and synthesized. Additionally, the bioassays revealed that the compound F15 demonstrated excellent antifungal activity against Sclerotinia sclerotiorum (S. sclerotiorum) in vitro, and the EC₅₀ value of that was 2.9 μg/mL, which is comparable with commonly used fungicides thifluzamide and fluopyram. Meanwhile, F15 demonstrated excellent curative and protective activity against S. sclerotiorum-infected cole in vivo. The scanning electron microscopy results showed that the hyphae of S. sclerotiorum treated with F15 became abnormally collapsed and shriveled, thereby inhibiting the growth of the hyphae. Furthermore, F15 exhibited favorable inhibition against the succinate dehydrogenase (SDH) of the S. sclerotiorum (IC₅₀ = 12.5 μg/mL), and the combination mode and binding ability between compound F15 and SDH were confirmed by molecular docking. In addition, compound F11 showed excellent nematicidal activity against Meloidogyne incognita at 200 μg/mL, the corrected mortality rate was 93.2%, which is higher than that of tioxazafen.     

Microwave Assistant Synthesis,Antifungal Activity and DFT Theoretical Study of Some Novel 1,2,4-Triazole Derivatives Containing Pyridine Moiety

In order to investigate the biological activity of novel 1,2,4-triazole compounds, seventeen novel 1,2,4-triazole derivatives containing pyridine moiety were synthesized under microwave assistant condition by multi-step reactions. The structures were characterized by ¹H NMR, MS and elemental analyses. The target compounds were evaluated for their fungicidal activities against Stemphylium lycopersici (Enjoji) Yamamoto, Fusarium oxysporum. sp. cucumebrium, and Botrytis cinerea in vivo, and the results indicated that some of the title compounds displayed excellent fungicidal activities. Theoretical calculation of the title compound was carried out with B3LYP/6-31G (d,p). The full geometry optimization was carried out using 6-31G (d,p) basis set, and the frontier orbital energy, atomic net charges were discussed, and the structure-activity relationship was also studied.     

Theoretical Studies on the Structures,Densities, Detonation Properties and Thermal Stability of Tris(triazolo)benzene and its Derivatives

To look for superior and safe high-energy density materials (HEDMs), tris(triazolo)benzene and its R = ?CN, ?NHNO₂, ?N(NO₂)₂, ?NH₂, ?N(NH₂NO₂), and ?N(NO₂ONO₂) derivatives were studied at the B3LYP/6-311G(d, p) level of density functional theory (DFT). The energy content of the molecules was evaluated by calculating standard heats of formation, using isodesmic reaction. The results showed that all tris(triazolo)benzene derivations had high and positive heat of formation. The bond dissociation energies and bond orders for the weakest bonds were analyzed to investigate the thermal stability of the tris(triazolo)benzene derivatives. Most tris(triazolo)benzene derivatives for Ring-R had large bond dissociation energies (BDEs) which were over 140kJ · mol^{? 1}except R = ?N(NO₂ONO₂), which showed that the tris(triazolo)benzene derivatives had good thermodynamic stability. Impact sensitivity was evaluated using frontier orbital energies and characteristic heights (H₅₀). These results indicated that incorporation with ?NH₂ is an effective means to decrease molecular sensitivity. Detonation velocities and pressures were estimated using modified Kamlet-Jacobs equations, based on the theoretical densities and heats of formation. These derivatives possess excellent detonation properties, for C, E, and, the detonation velocity are 9.38, and 9.98 km.s^?1, and the detonation pressure are 43.68, and 48.41Gpa, respectively, the detonation performances are better than cyclotetramethylenetetranitramine (HMX). The detonation character of A, B, D, G, and F also are very close to that of HMX. Taking detonation performance and stability into consideration, the most of tris(triazolo)benzene derivatives may be good candidates of high energies materials.