Abstract：
BACKGROUND: Cancer is a devastating disease. Many studies have shown that the primary causes of the aggressive and resistant types of cancer are the overexpression of receptors and growth factors, activation of oncogenes, and the inactivation of tumour suppressor genes. One such receptor is the epidermal growth factor receptor (EGFR), which is used as a drug target for the treatment of cancer.
OBJECTIVE: This study aimed to develop the new chemical entities of amide derivatives of chalcone as EGFR inhibitors using structure-activity relationship (SAR) studies, molecular docking, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) studies.
METHODS: New chemical entities (NCE) were designed based on literature findings. The Schrodinger 13.4 software was used for the molecular docking study. While Quickprop and Pro Tox-II online tools were used for ADME and toxicity prediction, respectively. .
RESULTS: In this work, all compounds were subjected to an in-silico ADMET analysis. After pharmacokinetic and toxicity profile predictions, the molecules were further analysed by molecular docking. As a result of molecular docking, molecules AC9 and AC19 showed comparable docking scores compared to standard Afatinib.
CONCLUSIONS: Molecules AC9 and AC19 showed good docking scores and a promising ADMET profile. In the future, these derivatives can be further evaluated for wet lab studies and determination of their biological activity.
OBJECTIVE: This study aimed to develop the new chemical entities of amide derivatives of chalcone as EGFR inhibitors using structure-activity relationship (SAR) studies, molecular docking, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) studies.
METHODS: New chemical entities (NCE) were designed based on literature findings. The Schrodinger 13.4 software was used for the molecular docking study. While Quickprop and Pro Tox-II online tools were used for ADME and toxicity prediction, respectively. .
RESULTS: In this work, all compounds were subjected to an in-silico ADMET analysis. After pharmacokinetic and toxicity profile predictions, the molecules were further analysed by molecular docking. As a result of molecular docking, molecules AC9 and AC19 showed comparable docking scores compared to standard Afatinib.
CONCLUSIONS: Molecules AC9 and AC19 showed good docking scores and a promising ADMET profile. In the future, these derivatives can be further evaluated for wet lab studies and determination of their biological activity.
摘要：
背景：癌症是一种毁灭性的疾病。许多研究表明，侵袭性和抗性癌症类型的主要原因是受体和生长因子的过度表达，癌基因的激活，以及肿瘤抑制基因的失活。一种这样的受体是表皮生长因子受体（EGFR），它被用作治疗癌症的药物靶标。
目的：本研究旨在利用构效关系（SAR）研究开发查尔酮酰胺衍生物作为EGFR抑制剂的新化学实体，分子对接,和ADMET(吸收，分布，新陈代谢，排泄,和毒性)研究。
方法：根据文献结果设计了新的化学实体（NCE）。采用Schrodinger13.4软件进行分子对接研究。虽然Quickprop和ProTox-II在线工具用于ADME和毒性预测，分别。
结果：在这项工作中，所有化合物均进行了计算机内ADMET分析.经过药代动力学和毒性预测，通过分子对接进一步分析分子。作为分子对接的结果,与标准阿法替尼相比,分子AC9和AC19显示出相当的对接评分.
结论：分子AC9和AC19显示出良好的对接评分和有希望的ADMET曲线。在未来,这些衍生物可以进一步评估湿实验室研究和测定其生物活性。
目的：本研究旨在利用构效关系（SAR）研究开发查尔酮酰胺衍生物作为EGFR抑制剂的新化学实体，分子对接,和ADMET(吸收，分布，新陈代谢，排泄,和毒性)研究。
方法：根据文献结果设计了新的化学实体（NCE）。采用Schrodinger13.4软件进行分子对接研究。虽然Quickprop和ProTox-II在线工具用于ADME和毒性预测，分别。
结果：在这项工作中，所有化合物均进行了计算机内ADMET分析.经过药代动力学和毒性预测，通过分子对接进一步分析分子。作为分子对接的结果,与标准阿法替尼相比,分子AC9和AC19显示出相当的对接评分.
结论：分子AC9和AC19显示出良好的对接评分和有希望的ADMET曲线。在未来,这些衍生物可以进一步评估湿实验室研究和测定其生物活性。
