Abstract

A growing incidence of drug resistance and tumour proliferation in non-small cell lung cancer escalates the urge for potential lead molecules. The plant-derived natural compounds have played a pivotal role in potential therapeutic agents owing to its versatility and low toxicity over the past decades. In this study, we have executed an in-silico based screening of 1574 natural compounds against the β-catenin via an integrated pharmacophore approach. Further investigation revealed that Mucronulatol and 7,4'-dihydroxyhomoisoflavanone possess a higher Glide score (−4.748 and −3.943 kcal/mol), binding affinity (−44.763 and −41.883 kcal/mol) alongside drug-likeness property than the iCRT5. Moreover, these compounds are reported to have cytotoxicity against lung cancer cell lines with an IC₅₀ value of 6.74 µM and 8.99 µM respectively. Furthermore, dynamic studies were employed to determine the structural stability and we hope that the lead molecules proposed in this study could effectively inhibit the β-catenin pathway associated with NSCLC.

摘要

非小细胞肺癌中耐药性和肿瘤增殖的发生率不断上升，这加剧了对潜在铅分子的渴望。在过去的几十年中，植物来源的天然化合物由于其多功能性和低毒性，在潜在的治疗剂中发挥了关键作用。在这项研究中，我们通过综合药效团方法对 1574 种天然化合物进行了基于 β-catenin的计算机筛选。进一步调查显示，与 iCRT5 相比，Mucronulatol 和 7,4'-二羟基高异黄烷酮具有更高的 Glide 评分（-4.748 和 -3.943 kcal/mol）、结合亲和力（-44.763 和 -41.883 kcal/mol）以及药物相似性。此外，据报道这些化合物对肺癌细胞系具有细胞毒性，IC ₅₀值分别为 6.74 µM 和 8.99 µM。此外，采用动态研究来确定结构稳定性，我们希望本研究中提出的先导分子能够有效抑制与 NSCLC 相关的 β-连环蛋白途径。