简介:癌症是一组庞大的疾病,包括不受控制地繁殖和生长的异常细胞,它是全球死亡的主要原因之一。诊断出几种类型的癌症,但是乳腺癌的发病率,尤其是绝经后的妇女,每天都在增加。用于治疗癌症的化学治疗剂通常与对宿主细胞的严重副作用有关。这导致寻找安全和潜在的替代品。因此,本研究已经进行了寻找新的生物活性分子,用绿原酸及其衍生物治疗乳腺癌。选择绿原酸是因为其在本领域中已知的活性。方法:对几种绿原酸衍生物进行分子对接等计算研究,吸收的测定,分布,新陈代谢,和排泄(ADME),像毒品一样,毒性,并预测物质的活性谱(PASS)以开发潜在的乳腺癌抑制剂。用于对接目的的蛋白质数据库(PDB)ID为7KCD,3ERT,6CHZ,3HB5,和1U72。结果:通过考虑各种参数对结果进行了详尽分析,比如对接得分,结合能,与结合袋中重要氨基酸残基相互作用的类型,ADME,和化合物的毒性数据。在所有选定的衍生物中,CgE18,CgE11,CgAm13,CgE16和CgE9有惊人的相互作用,优异的结合能,和更好的稳定性在活性位点的目标蛋白。化合物CgE18的对接评分为-11.63kcal/mol,-14.15kcal/mol,和-12.90kcal/mol对乳腺癌PDBID7KCD,3HB5,和1U72,分别。化合物CgE11对乳腺癌PDBID3ERT和6CHZ的对接评分分别为-10.77kcal/mol和-9.11kcal/mol,分别,而盐酸表柔比星的对接评分为-3.85kcal/mol,-6.4千卡/摩尔,-8.76千卡/摩尔,和-10.5千卡/摩尔对PDBID7KCD,3ERT,6CHZ,3HB5发现5-氟尿嘧啶的对接评分为-5.25kcal/mol,-3.43kcal/mol,-3.73千卡/摩尔,和-5.29kcal/mol对PDBID7KCD,3ERT,6CHZ,和3HB5,这表明设计的化合物比一些标准药物具有更好的对接评分。结论:考虑到分子对接的结果,药物相似性分析,吸收,分布,新陈代谢,排泄,和毒性(ADMET)评估,和PASS,可以得出结论,绿原酸衍生物有望作为治疗乳腺癌的有效抑制剂。
Introduction: Cancer is a vast group of diseases comprising abnormal cells that multiply and grow uncontrollably, and it is one of the top causes of death globally. Several types of cancers are diagnosed, but the incidence of breast cancer, especially in postmenopausal women, is increasing daily. Chemotherapeutic agents used to treat cancer are generally associated with severe side effects on host cells, which has led to a search for safe and potential alternatives. Therefore, the present research has been conducted to find novel bioactive molecules to treat breast cancer with chlorogenic acid and its derivatives. Chlorogenic acid was selected because of its known activity in the field. Methods: Several chlorogenic acid derivatives were subjected to computational studies such as molecular docking, determination of absorption, distribution, metabolism, and excretion (ADME), druglikeness, toxicity, and prediction of activity spectra for substances (PASS) to develop a potential inhibitor of breast cancer. The Protein Data Bank (PDB) IDs used for docking purposes were 7KCD, 3ERT, 6CHZ, 3HB5, and 1U72. Result: Exhaustive analysis of results has been conducted by considering various parameters, like docking score, binding energy, types of interaction with important amino acid residues in the binding pocket, ADME, and toxicity data of compounds. Among all the selected derivatives, CgE18, CgE11, CgAm13, CgE16, and CgE9 have astonishing interactions, excellent binding energy, and better stability in the active site of targeted proteins. The docking scores of compound CgE18 were -11.63 kcal/mol, -14.15 kcal/mol, and -12.90 kcal/mol against breast cancer PDB IDs 7KCD, 3HB5, and 1U72, respectively. The docking scores of compound CgE11 were -10.77 kcal/mol and -9.11 kcal/mol against breast cancer PDB IDs 3ERT and 6CHZ, respectively, whereas the docking scores of epirubicin hydrochloride were -3.85 kcal/mol, -6.4 kcal/mol, -8.76 kcal/mol, and -10.5 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5. The docking scores of 5-fluorouracil were found to be -5.25 kcal/mol, -3.43 kcal/mol, -3.73 kcal/mol, and -5.29 kcal/mol against PDB IDs 7KCD, 3ERT, 6CHZ, and 3HB5, which indicates the designed compounds have a better docking score than some standard drugs. Conclusion: Taking into account the results of molecular docking, drug likeness analysis, absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation, and PASS, it can be concluded that chlorogenic acid derivatives hold promise as potent inhibitors for the treatment of breast cancer.