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;乏氧是肿瘤组织的重要特点,而在肿瘤组织中高表达的Racl蛋白是与氧化还原过程密切相关的蛋白质,且参与肿瘤发展的多个过程。Racl抑制剂可有效抑制肿瘤细胞的侵润与发展。因此,有效的Racl抑制剂可成为潜在抗癌药物。目前能用于临床治疗肿瘤的Racl抑制剂鲜有报道。生物还原剂是一大类对乏氧细胞有特异毒性的化合物,可以靶向作用于乏氧细胞,抑制乏氧肿瘤细胞的生长。本文根据Racl的三维结构,利用虚拟筛选软件PyRx,在化合物库中对约1.5万个硝基杂环化合物、芳香氮氧化合物、脂肪氮氧化合物、醌类化合物等生物还原剂进行筛选,根据结合能、结合位点、结合模式等条件筛选出6个候选Racl抑制剂,为靶向乏氧肿瘤细胞的生物还原剂的开发、构效关系研究提供理论依据。
Hypoxia is an important feature of tumor tissue. Rac1 protein highly expressed in tumor tissues is a protein closely related to the redox process and involved in multiple processes of tumor development. Racl inhibitors can effectively inhibit the invasion and development of tumor cells. Therefore, potent Racl inhibitors can be potential anticancer drugs. Racl inhibitors currently available for the clinical treatment of tumors are rarely reported. Bioreductive agents are a large group of compounds that are specifically toxic to hypoxic cells and can target to hypoxic cells and inhibit the growth of hypoxic tumor cells. According to the three-dimensional structure of Racl, we use the virtual screening software PyRx to screen about 15,000 nitro-heterocyclic compounds, aromatic nitroxides, aliphatic nitroxides and quinone compounds in the compound library, Six candidate Racl inhibitors were screened out for their binding sites, binding sites and binding modes to provide a theoretical basis for the development and structure-activity relationship of biological reductants targeting hypoxic tumor cells.