抗血管生成拟肽的设计及其生物活性的实验评估

Design of Anti-Angiogenic Peptidomimetics and Evaluation their Biological Activity by Assays.

作者信息

Ghadam Mona, Sardari Soroush, Shokrgozar Mohammad Ali, Mahdavi Mahdiyeh Sadat

机构信息

Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Avicenna J Med Biotechnol. 2020 Apr-Jun;12(2):91-98.

PMID:32431793

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7229457/

Abstract

BACKGROUND

One of the important therapeutic approaches in cancer field is development of compounds which can block the initial tumor growth and the progression of tumor metastasis with no side effects. Thus, the recent study was carried out to design anti-VEGFR2-peptidomimetics as the most significant factor of angiogenesis process- and evaluate their biological activity by assays.

METHODS

We designed anti-VEGFR2 peptidomimetics with anti-angiogenic activity, including compound P (lactam derivative) and compound T (indole derivative) by using in silico methods. Then, the inhibitory activity on angiogenesis was evaluated by using angiogenesis specific assays such as Human Umbilical Vein Endothelial Cell (HUVEC) proliferation, tube formation in Matrigel, MTT and Real-Time PCR. IC50 values of the compounds were also determined by cytotoxicity plot in MTT assay.

RESULTS

Compounds P and T inhibited HUVEC cell proliferation and viability in a dose-dependent manner. The IC50 for compound T and compound P in HUVEC cell line were 113 and 115 , respectively. Tube formation assay revealed that both compounds can inhibit angiogenesis effectively. The results of Real-Time PCR also showed these compounds are able to inhibit the expression of gene in HUVEC cell line.

CONCLUSION

Our study suggested that compounds P and T may act as therapeutic molecules, or lead compounds for development of angiogenesis inhibitors in VEGF-related diseases.

摘要

背景

癌症领域重要的治疗方法之一是开发能够在无副作用的情况下阻断肿瘤初始生长和转移进程的化合物。因此，开展了近期这项研究，以设计作为血管生成过程中最重要因素的抗血管内皮生长因子受体2（VEGFR2）拟肽，并通过实验评估它们的生物活性。

方法

我们采用计算机模拟方法设计了具有抗血管生成活性的抗VEGFR2拟肽，包括化合物P（内酰胺衍生物）和化合物T（吲哚衍生物）。然后，通过使用血管生成特异性实验，如人脐静脉内皮细胞（HUVEC）增殖、基质胶中的管腔形成、MTT和实时定量聚合酶链反应（Real-Time PCR），评估对血管生成的抑制活性。还通过MTT实验中的细胞毒性图确定化合物的半数抑制浓度（IC50）值。