Abstract

Angiogenesis is an important process that plays an active role in tumorigenesis. VEGFRs, a member of the tyrosine kinase receptor family involved in this process, is known as the receptor for VEGF ligands in tumor cells. c-Src is an adapter protein located downstream of VEGFRs and plays a role in angiogenic signaling. SPARC protein has recently been shown to play a role in metastasis in various types of cancer. In this study, inhibition of angiogenesis via extracellular matrix and VEGF/VEGFRs is aimed. Momordica charantia; is a valuable plant used quite often in traditional medicine. Triterpenes from various regions of plant appear to be promising in in vitro cancer-related studies. In our study; literature was searched to identify possible triterpenes in this plant; triterpenes in fruit and seed were selected. The 2D and 3D structure files of these triterpenes were obtained from PubChem. The structure files of the ligands were prepared with various programs and converted to the appropriate file format. X-ray diffraction structures of proteins were obtained from RCSB PDB. These structure files were made suitable for molecular docking studies. Docking and scoring were performed with the Vina program to select the appropriate poses. According to the in silico analysis; It has been found that various triterpenes that can be obtained from M. charantia plant may inhibit VEGFRs, SPARC, and c-Src proteins. These results show that these triterpenes are promising in terms of new natural therapeutic routes and drug candidates for aggressive cancer therapy.

中文翻译：

---

苦瓜中三萜与参与血管化的蛋白质相互作用的计算机评估

摘要

血管生成是一个重要过程，在肿瘤发生中发挥积极作用。VEGFR 是参与这一过程的酪氨酸激酶受体家族的成员，被称为肿瘤细胞中 VEGF 配体的受体。c-Src 是一种位于 VEGFR 下游的衔接蛋白，在血管生成信号传导中发挥作用。SPARC 蛋白最近被证明在多种癌症的转移中发挥作用。本研究的目的是通过细胞外基质和 VEGF/VEGFR 抑制血管生成。苦瓜；是一种在传统医学中经常使用的有价值的植物。来自植物不同区域的三萜似乎在体外癌症相关研究中很有前景。在我们的研究中；检索文献以鉴定该植物中可能存在的三萜类化合物；选择果实和种子中的三萜。这些三萜的 2D 和 3D 结构文件是从 PubChem 获得的。使用各种程序准备配体的结构文件并转换为适当的文件格式。从 RCSB PDB 获得蛋白质的 X 射线衍射结构。这些结构文件适合分子对接研究。使用 Vina 程序进行对接和评分，以选择合适的姿势。根据计算机分析；已经发现，从苦瓜植物中获得的多种三萜可以抑制VEGFR、SPARC和c-Src蛋白。这些结果表明，这些三萜类化合物在新的天然治疗途径和侵袭性癌症治疗的候选药物方面具有广阔的前景。