Department of Chemistry, AISSMS College of Pharmacy, Kennedy Road, Pune 01, India.
Curr Drug Discov Technol. 2024;21(3):9-19. doi: 10.2174/0115701638263890231027071518.
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.
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.
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. .
In this work, all compounds were subjected to an 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.
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.
癌症是一种毁灭性的疾病。许多研究表明，导致癌症侵袭性和耐药性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。表皮生长因子受体（EGFR）就是这样一种受体，它被用作癌症治疗的药物靶点。
本研究旨在通过构效关系（SAR）研究、分子对接和 ADMET（吸收、分布、代谢、排泄和毒性）研究，开发查尔酮酰胺衍生物作为 EGFR 抑制剂的新化学实体。
根据文献发现设计新的化学实体（NCE）。使用 Schrodinger 13.4 软件进行分子对接研究。同时使用 Quickprop 和 Pro Tox-II 在线工具分别进行 ADME 和毒性预测。
在这项工作中，所有化合物都进行了 ADMET 分析。在进行药代动力学和毒性特征预测后，进一步通过分子对接对分子进行分析。分子对接的结果表明，与标准药物阿法替尼相比，分子 AC9 和 AC19 具有相当的对接评分。
分子 AC9 和 AC19 表现出良好的对接评分和有前途的 ADMET 特征。在未来，这些衍生物可以进一步进行湿实验室研究，并确定其生物活性。
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