Megantara Sandra, Wathoni Nasrul, Mohammed Ahmed Fouad Abdelwahab, Suhandi Cecep, Ishmatullah Maryam H, Putri Melisa F F D
Department of Pharmaceutical Analysis and Medicinal Chemistry, Universitas Padjadjaran, Sumedang 45363, West Java, Indonesia.
Department of Pharmaceutics and Pharmaceutical Technology, Universitas Padjadjaran, Sumedang 45363, West Java, Indonesia.
Polymers (Basel). 2022 Jul 5;14(13):2747. doi: 10.3390/polym14132747.
Breast cancer is a type of cancer with the highest prevalence worldwide. Almost 10-30% of breast cancer cases are diagnosed as positive for HER2 (human epidermal growth factor receptor 2). The currently available treatment methods still exhibit many shortcomings such as a high incidence of side effects and treatment failure due to resistance. This in silico study aims to simulate α-mangostin and chitosan combination conjugated to trastuzumab formulation against HER2 as an effort to improve breast cancer patient therapy. This molecular docking simulation was done through using PatchDock Server. The materials used including the two-dimensional structure of α-mangostin, chitosan, and sodium tripolyphosphate from the PubChem database; trastuzumab FASTA sequence from the DrugBank database; and HER2 structure obtained from a crystal complex with PDB ID: 1N8Z. The results indicated that the particle of α-mangostin and chitosan combinations interacted mostly with the crystallizable fragment (Fc region) of trastuzumab in the conjugation process. The conjugation of trastuzumab to the particle of a combination of α-mangostin and chitosan resulted in the greatest increase in the binding score of the smallest-sized particles (50 Å) with an increase in the score of 3828 and also gave the most similar mode of interaction with trastuzumab. However, the conjugation of trastuzumab eliminated the similarity of the mode of interaction and increased the value of atomic contact energy. Thus, a cominbation of α-mangostin and chitosan conjugated to a trastuzumab formulation was predicted can increase the effectiveness of breast cancer therapy at a relatively small particle size but with the consequence of decreasing atomic contact energy.
乳腺癌是全球患病率最高的癌症类型。几乎10%-30%的乳腺癌病例被诊断为HER2（人表皮生长因子受体2）阳性。目前可用的治疗方法仍存在许多缺点，如副作用发生率高以及因耐药导致治疗失败。这项计算机模拟研究旨在模拟与曲妥珠单抗制剂共轭的α-山竹素和壳聚糖组合，以提高乳腺癌患者的治疗效果。这种分子对接模拟是通过使用PatchDock服务器完成的。所使用的材料包括来自PubChem数据库的α-山竹素、壳聚糖和三聚磷酸钠的二维结构；来自DrugBank数据库的曲妥珠单抗FASTA序列；以及从PDB ID为1N8Z的晶体复合物中获得的HER2结构。结果表明，在共轭过程中，α-山竹素和壳聚糖组合颗粒主要与曲妥珠单抗的可结晶片段（Fc区）相互作用。曲妥珠单抗与α-山竹素和壳聚糖组合颗粒的共轭导致最小尺寸颗粒（50 Å）的结合分数增加最多，分数增加了3828，并且与曲妥珠单抗的相互作用模式也最为相似。然而，曲妥珠单抗的共轭消除了相互作用模式的相似性并增加了原子接触能的值。因此，预测与曲妥珠单抗制剂共轭的α-山竹素和壳聚糖组合在相对较小的颗粒尺寸下可以提高乳腺癌治疗的有效性，但会导致原子接触能降低。
