Evaluation of the Antioxidant Properties and Cytotoxic Activity of 1,3-dioxolane Derivatives Imidazole

S. S. Zykova, M. V. Shustov, V. Talismanov
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Abstract

Introduction. Modern chemotherapy widely considers the role of antioxidant and pro-oxidant methods in the treatment of oncologic pathologies. The use of agents that cause an increase of ROS is a relevant way to destroy tumors. At the same time, there is evidence of the ability of some antioxidants to lead to the cancer cells apoptosis through the generation of free radical forms of oxygen due to disruption of cellular homeostasis. The combination of the «Ecolum» biosensor using technique, antiradical activity data, and information about the cytotoxicity of compounds used in the study allows us to consistently conduct low-cost screening of as antioxidant, as antiradical activities and potentially reduce the required number of expensive cytotoxicity determinations using tumor cells.Aim. The main target of our work is the evaluation of antioxidant and cytotoxic activities of 1,3-dioxolane derivatives of imidazole using antioxidant, antiradical and cytotoxicity tests in vitro.Materials and methods. To carry out this study, 1,3-dioxolane derivatives of imidazole were obtained. The antiradical tests was performed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Antioxidant properties were assessed within the Ecolum biosensor in the state of oxidative stress. Cytotoxic activity was assessed in GIST-T1 cell culture using the MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide).Results and discussion. Data from studies of the antioxidant activity of substances using the «Ecolum» biosensor showed varying degrees of damage to the biosensor in the absence of antioxidant action. The antiradical potential, initially used to reveal a possible mechanism of antioxidant action, actually demonstrated a possible mechanism of toxic action of substance 2c due to its antiradical effect comparable to the standard (Trolox), but the substance has the highest cytotoxicity. However, the properties of substance 2a shows that the direct correlation discussed earlier is not found in all cases.Conclusion. The asessment of the antioxidant properties and cytotoxic activity of 1,3-dioxolane derivatives of imidazole demonstrated the relevance of further searching for connections between the results of substances binding with the Ecolum biosensor under conditions of oxidative stress, their antiradical potential and cytotoxic properties. This combination of tests will potentially reduce the cost of screening through the use of an available biosensor, establish a possible mechanism of action aimed at redox balance, and confirm previously obtained data through the use of tumor cell culture.
评估 1,3-二氧戊环衍生物咪唑的抗氧化性和细胞毒性活性
导言。现代化疗广泛考虑抗氧化剂和促氧化剂方法在治疗肿瘤病症中的作用。使用导致 ROS 增加的药物是摧毁肿瘤的一种相关方法。同时,有证据表明,一些抗氧化剂能够通过产生自由基形式的氧来破坏细胞的平衡,从而导致癌细胞凋亡。结合使用 "Ecolum "生物传感器技术、抗自由基活性数据和研究中使用的化合物的细胞毒性信息,我们可以持续进行低成本的抗氧化剂和抗自由基活性筛选,并有可能减少使用肿瘤细胞进行昂贵的细胞毒性测定所需的次数。我们工作的主要目标是通过体外抗氧化、抗自由基和细胞毒性测试,评估咪唑的 1,3- 二氧戊环衍生物的抗氧化和细胞毒性活性。为了开展这项研究,我们获得了咪唑的 1,3-二氧戊环衍生物。抗自由基测试采用 DPPH(2,2-二苯基-1-苦基肼)法进行。在氧化应激状态下,通过 Ecolum 生物传感器对抗氧化特性进行了评估。使用 MTT 试验(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑)评估 GIST-T1 细胞培养的细胞毒性活性。使用 "Ecolum "生物传感器对物质的抗氧化活性进行的研究数据显示,在没有抗氧化作用的情况下,生物传感器会受到不同程度的损坏。最初用来揭示可能的抗氧化作用机制的抗自由基电位实际上证明了物质 2c 可能的毒性作用机制,因为它的抗自由基效果与标准物质(三氯氧磷)相当,但该物质的细胞毒性最高。不过,物质 2a 的特性表明,并非在所有情况下都存在前面讨论的直接相关性。对咪唑的 1,3-二氧戊环衍生物的抗氧化特性和细胞毒性活性的评估表明,进一步寻找在氧化应激条件下与 Ecolum 生物传感器结合的物质的结果、其抗自由基潜力和细胞毒性特性之间的联系具有重要意义。通过使用现有的生物传感器,这种测试组合将有可能降低筛选成本,建立针对氧化还原平衡的可能作用机制,并通过使用肿瘤细胞培养证实之前获得的数据。
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