CD151 has been recognized as a prognostic marker, the therapeutic target of breast cancers, but less explored for small molecule inhibitors due to lack of a validated model. The 3-D structure of CD151 large extracellular loop (LEL) was modeled using the LOMETS server and validated by the Ramachandran plot. The validated structure was employed for molecular docking and structure-based pharmacophore analysis. Druglikeness was evaluated by the ADMET description protocol. Antiproliferative activity was evaluated by MTT, BrdU incorporation, flow cytometry, and cell death ELISA^PLUS assay. This study predicted the best model for CD151-LEL with 94.1% residues in favored regions and Z score −2.79 kcal/mol using the threading method. The web-based receptor cavity method identified one functional target site, which was suitable for the binding of aromatic and heterocyclic compounds. Molecular docking study identified pyrocatechol (PCL) and 5-fluorouracil (FU) as potential leads of CD151-LEL. The pharmacophore model identified interaction points of modeled CD151-LEL with PCL and FU. Also, the analysis of ADMET properties revealed the drug-likeness of PCL and FU. The viability of MDA-MB 231 cells was significantly reduced with PCL and FU but less affected MCF-12A, normal healthy breast epithelial cell line. With 50% toxic concentration, both PCL and FU significantly inhibited 82.46 and 87.12% proliferation, respectively, of MDA-MB 231 cells by altering morphology and inducing G1 cell cycle arrest and apoptosis. In addition, PCL and FU inhibited the CD151 expression by 4.5-and 4.8-folds, respectively. This study suggests the further assessment of pyrocatechol as a potential lead of CD151 in breast cancer at the molecular level.

CD151被公认为是乳腺癌的预后指标，是乳腺癌的治疗靶标，但由于缺乏经过验证的模型，对小分子抑制剂的研究较少。使用LOMETS服务器对CD151大细胞外环（LEL）的3-D结构进行了建模，并通过Ramachandran图进行了验证。经验证的结构用于分子对接和基于结构的药效团分析。通过ADMET描述方案评估药物相似性。通过MTT，BrdU掺入，流式细胞术和细胞死亡ELISA ^PLUS评估抗增殖活性分析。这项研究使用穿线方法预测了CD151-LEL的最佳模型，其在有利区域的残基为94.1％，Z评分为-2.79 kcal / mol。基于网络的受体腔法确定了一个功能性目标位点，该位点适用于芳香族和杂环化合物的结合。分子对接研究确定了邻苯二酚（PCL）和5-氟尿嘧啶（FU）是CD151-LEL的潜在先导。药效团模型确定了建模的CD151-LEL与PCL和FU的相互作用点。同样，对ADMET特性的分析揭示了PCL和FU的药物相似性。PCL和FU可以显着降低MDA-MB 231细胞的活力，但对MCF-12A（正常的健康乳腺上皮细胞系）的影响较小。毒性浓度为50％时，PCL和FU分别分别显着抑制82.46和87.12％的增殖，MDA-MB 231细胞通过改变形态并诱导G1细胞周期阻滞和凋亡而发生凋亡。此外，PCL和FU分别抑制CD151表达4.5倍和4.8倍。这项研究建议在分子水平上进一步评估邻苯二酚作为乳腺癌中CD151的潜在先导。