In silico Activity and Target Prediction Analyses of Three Triazolothiadiazine Derivatives

IF 0.3 4区 医学 Q4 Medicine
Ceren Sucularlı, B. Tozkoparan, S. P. Aytaç
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引用次数: 0

Abstract

Objective: Polypharmacology, interaction of one drug with multiple targets, emerged as an effective approach in drug discovery and development. Bioinformatics and cheminformatics methods are essential tools for determination of polypharmacological profiles of newly synthesized or known compounds and drugs. Previously, three novel triazolothiadiazine derivatives; 1h, 3c and 3h, have been shown to induce apoptosis and cause cell cycle arrest on liver cancer cells. The aim of this study is to find possible action mechanisms and potential targets for these three triazolothiadiazine derivatives, and to investigate their potential as new therapeutic agents by using computational methods. Materials and Methods: PASS software was used to identify biological activities and Swiss Target Prediction and BindingDB databases to predict potential targets for 1h, 3c and 3h. PDE4A, ALR and DUSP1 proteins were selected for molecular docking analysis following the protein modeling of the three proteins. Results: Activity prediction results show that 1h, 3c and 3h might have phosphatase and signal transduction pathway inhibitor, hepatocyte growth factor antagonist, anti-inflammatory and antifungal activities. These derivatives are predicted as inhibitors of several phosphodiesterases by activity and target prediction tools. Conclusion: Based on prediction and molecular docking results, it is proposed that these compounds may have therapeutic properties through new predicted targets.
三氮唑噻二嗪衍生物的硅活性及靶标预测分析
目的:多药理学,即一种药物与多个靶点的相互作用,已成为药物发现和开发的有效途径。生物信息学和化学信息学方法是确定新合成或已知化合物和药物的多药理学特征的重要工具。此前,三种新型三唑噻二嗪衍生物;1h、3c和3h可诱导肝癌细胞凋亡并导致细胞周期阻滞。本研究的目的是寻找这三种三氮唑噻二嗪衍生物可能的作用机制和潜在的靶点,并利用计算方法研究它们作为新型治疗剂的潜力。材料与方法:采用PASS软件鉴定生物活性,Swiss Target Prediction和BindingDB数据库预测1h、3c和3h的潜在靶点。在对三种蛋白进行蛋白建模后,选择PDE4A、ALR和DUSP1蛋白进行分子对接分析。结果:活性预测结果显示,1h、3c和3h可能具有磷酸酶和信号转导途径抑制剂、肝细胞生长因子拮抗剂、抗炎和抗真菌活性。这些衍生物通过活性和靶标预测工具被预测为几种磷酸二酯酶的抑制剂。结论:基于预测和分子对接结果,提出这些化合物可能通过新的预测靶点具有治疗作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Acta Medica Mediterranea
Acta Medica Mediterranea 医学-医学:内科
自引率
0.00%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Acta Medica Mediterranea is an indipendent, international, English-language, peer-reviewed journal, online and open-access, designed for internists and phisicians. The journal publishes a variety of manuscript types, including review articles, original research, case reports and letters to the editor.
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