Jihad Marwan I, Mahdi Monther F
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mustansiriyah, Baghdad, Iraq.
J Pharm Bioallied Sci. 2023 Jul;15(Suppl 2):S1023-S1026. doi: 10.4103/jpbs.jpbs_244_23. Epub 2023 Jul 11.
Cancer is a disease triggered by an uncontrolled growth of a group of cells usually from a single cell. Chemotherapy is a common and systematic therapy that involves the use of anticancer drugs also known as chemotherapeutical agents to treat cancer. Tyrosine kinases are a subset of protein kinases that are a family of over 90 enzymes that selectively phosphorylate tyrosine residues in various substrates. Receptors with internal tyrosine kinase activity mediate the actions of several growth factors, differentiation factors, and hormones, resulting in the reproduction and differentiation of the affected cells. In the fight against cancer, the platelet-derived growth factor receptor has emerged as a novel target via inhibition of this receptor resulting in the inhibition of tyrosine kinase cascade. Docking investigations were conducted using the Genetic Optimization for Ligand Docking (GOLD) Suite (v. 5.7.1) from the Cambridge Crystallographic Data Center. A high-definition X-ray crystallography of the platelet-derived growth factor protein [Protein Data Bank (PDB) ID 6JOL] was downloaded from the website PDB with a resolution of 2 A. Compounds II, III, VII, and VIII have greater binding energies than the GOLD standard medication sorafenib, which gives Piecewise Linear Potential (PLP) fitness value (85.3). Other ligands exhibit good inhibitory action and docking scores comparable to that of the reference ligand sorafenib.
癌症是一种由一组通常源自单个细胞的细胞不受控制地生长所引发的疾病。化疗是一种常见的系统性治疗方法，涉及使用抗癌药物（也称为化疗药物）来治疗癌症。酪氨酸激酶是蛋白激酶的一个子集，蛋白激酶是一个由90多种酶组成的家族，可选择性地使各种底物中的酪氨酸残基磷酸化。具有内在酪氨酸激酶活性的受体介导多种生长因子、分化因子和激素的作用，导致受影响细胞的增殖和分化。在抗癌斗争中，血小板衍生生长因子受体已成为一个新的靶点，通过抑制该受体可导致酪氨酸激酶级联反应受到抑制。使用剑桥晶体学数据中心的遗传配体对接优化（GOLD）套件（版本5.7.1）进行对接研究。从蛋白质数据银行（PDB）网站下载了血小板衍生生长因子蛋白的高分辨率X射线晶体学数据[PDB ID 6JOL]，分辨率为2埃。化合物II、III、VII和VIII的结合能比GOLD标准药物索拉非尼更高，索拉非尼的逐段线性势能（PLP）适应度值为85.3。其他配体表现出良好的抑制作用，对接分数与参考配体索拉非尼相当。
