Rhazi Yassine, Sghyar Riham, Deak Noemi, Es-Sounni Bouchra, Rossafi Bouchra, Soran Albert, Laghmari Mustapha, Arzine Azize, Nakkabi Asmae, Hammani Khalil, Chtita Samir, M Alanazi Mohammed, Nemes Gabriela, El Yazidi Mohamed
Engineering Laboratory of Organometallic, Materials and Environment, Faculty of Sciences Dhar EL Mahraz, Sidi Mohamed Ben Abdellah University, P.O. Box 1796, Atlas, Fez 30000, Morocco.
Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University, 11 Arany Janos, 400028 Cluj-Napoca, Romania.
Pharmaceuticals (Basel). 2024 Oct 18;17(10):1390. doi: 10.3390/ph17101390.
: This research centers on the development and spectroscopic characterization of new quinazolin-4(3H)-one-isoxazole derivatives (). The aim was to investigate the regioselectivity of the 1,3-dipolar cycloaddition involving arylnitriloxides and N-propargylquinazolin-4(3H)-one, and to assess the antioxidant properties of the synthesized compounds. The synthetic approach started with the alkylation of quinazolin-4(3H)-one using propargyl bromide, followed by a 1,3-dipolar cycloaddition reaction. : The structural identification of the products was performed using various spectroscopic methods, such as IR, 1H, 13C, and HMBC NMR, HRMS, and single-crystal X-ray diffraction. To further examine the regioselectivity of the cycloaddition, Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d) level were employed. Additionally, the antioxidant potential of the compounds was tested in vitro using DPPH (2,2-Diphenyl-1-picrylhydrazyl)radical scavenging assays. The reaction selectively produced 3,5-disubstituted isoxazoles, with the regiochemical outcome being independent of the substituents on the phenyl ring. : Theoretical calculations using DFT were in agreement with the experimental results, revealing activation energies of -81.15 kcal/mol for P-1 and -77.32 kcal/mol for P-2, favoring the formation of P-1. An analysis of the Intrinsic Reaction Coordinate (IRC) confirmed that the reaction proceeded via a concerted but asynchronous mechanism. The antioxidant tests demonstrated that the synthesized compounds exhibited significant radical scavenging activity, as shown in the DPPH assay. The 1,3-dipolar cycloaddition of arylnitriloxides with N-propargylquinazolin-4(3H)-one successfully resulted in novel 3,5-disubstituted isoxazoles. : The experimental findings were well-supported by theoretical predictions, and the antioxidant assays revealed strong activity, indicating the potential for future biological applications of these compounds.
本研究聚焦于新型喹唑啉 - 4(3H)-酮 - 异恶唑衍生物（）的开发与光谱表征。目的是研究涉及芳基硝酮和N - 炔丙基喹唑啉 - 4(3H)-酮的1,3 - 偶极环加成反应的区域选择性，并评估合成化合物的抗氧化性能。合成方法始于使用炔丙基溴对喹唑啉 - 4(3H)-酮进行烷基化，随后进行1,3 - 偶极环加成反应。通过各种光谱方法对产物进行结构鉴定，如红外光谱（IR）、1H、13C和HMBC核磁共振（NMR）、高分辨质谱（HRMS）以及单晶X射线衍射。为进一步研究环加成反应的区域选择性，采用了B3LYP/6 - 31G(d)水平的密度泛函理论（DFT）计算。此外，使用2,二苯基 - 1 - 苦基肼（DPPH）自由基清除试验在体外测试了化合物的抗氧化潜力。该反应选择性地生成了3,5 - 二取代异恶唑，区域化学结果与苯环上的取代基无关。DFT理论计算与实验结果一致，显示P - 1的活化能为 - 81.15千卡/摩尔，P - 2的活化能为 - 77.32千卡/摩尔，有利于P - 1的形成。对内在反应坐标（IRC）的分析证实该反应通过协同但非同步的机制进行。抗氧化测试表明，合成的化合物在DPPH试验中表现出显著的自由基清除活性。芳基硝酮与N - 炔丙基喹唑啉 - 4(3H)-酮的1,3 - 偶极环加成反应成功生成了新型3,5 - 二取代异恶唑。实验结果得到理论预测的有力支持，抗氧化试验显示出强大的活性，表明这些化合物未来在生物应用方面具有潜力。
