Meshcheryakova Svetlana, Kayumova Aliya, Kang Yang, Shumadalova Alina, Vinogradova Yulia, Khuzin Dinislam, Ziyakaeva Klara, Kiseleva Olga, Gabdulkhakova Irina, Beylerli Ozal, Gareev Ilgiz, Sufianov Albert, Sufianova Galina, Ahmad Aamir, Yang Guang, Guo Zidan
Department of General Chemistry, Bashkir State Medical University, Ufa, Russian Federation.
Department of Normal Physiology, Bashkir State Medical University, Ufa, Russian Federation.
Curr Med Chem. 2023;30(17):1993-2004. doi: 10.2174/0929867329666220805125638.
It is relevant to study the general patterns and identify non-specific mechanisms of body protective and adaptive reactions violation, which can lead to the various pathological processes and develop principles for the correction of these disorders. One of the therapy and prevention directions is the search for new medicines. In recent years, new derivatives of pyrimidine bases have been synthesized and studied. Pyrimidine-based medicines have a membrane-stabilizing and immunomodulatory effect and can normalize metabolic disorders and increase the oxidative activity of leukocytes. Disruption of the free radical oxidation processes, the generation of reactive oxygen species and lipid peroxidation, including in whole blood and bone marrow, has gained importance in recent years.
Each reaction was monitored by thin layer chromatography. H, C, and N NMR spectra were recorded (chemical shifts were expressed as δ-values). We studied the effect of 6-methyl-3-(thietan- 3-yl)pyrimidine-2,4(1H,3H)-dione on the generation of reactive oxygen species (ROS) in the whole blood and bone marrow using the study of whole blood spontaneous and stimulated chemiluminescence (CL). CL methods make it possible to quickly and easily assess the studied material (whole blood, bone marrow) effect on free radical oxidation. Using CL methods, it is possible to reveal the presence of medicines' pro- or antioxidant properties, opening up new possibilities in the search for substances with antioxidant properties and comparing their activity.
Alkylation of 6-methylpyrimidine-2,4(1H,3H)-dione by 2-chloromethylthiirane in protic solvents in the presence of alkali leads to the formation of an N-thietane derivative. NMR spectroscopy showed that 6-methylpyrimidine-2,4(1H,3H)-dione was alkylated at position 3. The oxidation reactions of N-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione were studied, and it was determined that, depending on the excess of the oxidizing agent and the duration of the process, N-(1-oxothietan-3-yl)- or N-(1,1-- dioxothietan-3-yl)pyrimidine-2,4(1H,3H)-diones were formed. The effects of free radical oxidation processes of new biologically active pyrimidine-2,4(1H,3H)-diones were studied.
New pyrimidine-2,4(1H,3H)-diones increase the general adaptive capabilities of the body and have protective effects in extreme conditions.
研究身体保护和适应性反应破坏的一般模式并确定非特异性机制具有重要意义，这些机制可能导致各种病理过程，并制定纠正这些紊乱的原则。治疗和预防方向之一是寻找新药。近年来，已合成并研究了嘧啶碱基的新衍生物。基于嘧啶的药物具有膜稳定和免疫调节作用，可使代谢紊乱正常化并增加白细胞的氧化活性。近年来，自由基氧化过程的破坏、活性氧的产生和脂质过氧化，包括全血和骨髓中的脂质过氧化，已变得至关重要。
通过薄层色谱监测每个反应。记录了氢、碳和氮核磁共振光谱（化学位移以δ值表示）。我们使用全血自发和刺激化学发光（CL）研究了6-甲基-3-（硫杂环丁烷-3-基）嘧啶-2,4（1H,3H）-二酮对全血和骨髓中活性氧（ROS）产生的影响。CL方法使快速轻松地评估所研究物质（全血、骨髓）对自由基氧化的影响成为可能。使用CL方法，可以揭示药物的促氧化或抗氧化特性，为寻找具有抗氧化特性的物质并比较它们的活性开辟了新的可能性。
在质子溶剂中，在碱存在下，2-氯甲基硫杂环丙烷对6-甲基嘧啶-2,4（1H,3H）-二酮进行烷基化反应，生成N-硫杂环丁烷衍生物。核磁共振光谱表明6-甲基嘧啶-2,4（1H,3H）-二酮在3位发生了烷基化。研究了N-（硫杂环丁烷-3-基）嘧啶-2,4（1H,3H）-二酮的氧化反应，并确定根据氧化剂的过量情况和反应过程的持续时间，会形成N-（1-氧代硫杂环丁烷-3-基）-或N-（1,1-二氧代硫杂环丁烷-3-基）嘧啶-2,4（1H,
新的嘧啶-2,4（1H,3H）-二酮可提高机体的一般适应能力，并在极端条件下具有保护作用。
