猫抑制剂设计与开发引起了人们对其在治疗不同癌症类型，包括肺癌方面的潜在治疗应用的兴趣。本研究调查了异碳槿皮素-3-O-鼠李糖苷对猫蛋白酶D（CATD）的结合亲和力。分子对接和比色实验显示出强烈的结合亲和力(-7.8 kcal/mol)。分子动力学（MD）模拟证实该复合物的稳定性，而酶抑制研究显示无细胞条件下的抑制浓度（IC50）值为35.14 ± 6.08 μM，在细胞基础上为16.00 ± 3.48 μM。表达分析表明CATD下调（折叠变化1.35倍）。异碳槿皮素在NCIH-520细胞上显示出抗增殖效果[在磺睛亮B（SRB）中的IC50为64.11 μM，在3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物（MTT）中为24.44 μM]，但对健康的CHANG细胞没有影响。它还延长了G2/M期（10 μM：1.19倍；100 μM：1.13倍）并增加了亚二倍体人口（1.35倍）。根据SwissADME程序的计算，可以假设异碳槿皮素不是细胞色素P450（CYPs）抑制剂，符合Ghose准则，并且不透过血脑屏障（BBB），暗示它是一种安全的分子。总之，我们的发现为异碳槿皮素及其类似物被用于治疗CATD介导的肺癌预防奠定了基础。版权所有 © 2023. Elsevier Ltd.发表。

Cathepsin-D (CATD) inhibitor design and development have drawn interest due to their potential therapeutic applications in managing different cancer types, including lung cancer. This study investigated myricitrin, a flavonol-3-O-rhamnoside, for its binding affinity to CATD. Molecular docking and colorimetric experiments revealed strong binding affinity (-7.8 kcal/mol). Molecular dynamics (MD) simulation confirmed the complex's stability, while enzyme inhibition studies showed inhibitory concentration (IC50) values of 35.14 ± 6.08 μM (cell-free) and 16.00 ± 3.48 μM (cell-based). Expression analysis indicated CATD downregulation (fold change 1.35). Myricitrin demonstrated antiproliferative effects on NCIH-520 cells [IC50: 64.11 μM in Sulphorhodamine B (SRB), 24.44 μM in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromi (MTT)], but did not affect healthy CHANG cells. It also prolonged the G2/M phase (10 μM: 1.19-fold; 100 μM: 1.13-fold) and increased sub-diploid population (1.35-fold). Based on calculations with the SwissADME program, it can be assumed that myricitirn is not a cytochrome p450s (CYPs) inhibitor, followed the rule of Ghose and was not permeable to the blood-brain barrier (BBB), suggesting is a safe molecule. In summary, our findings establish the foundation for myricitrin and its analogues to be used therapeutically in CATD-mediated lung cancer prevention.Copyright © 2023. Published by Elsevier Ltd.