Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt.
Biochemistry & Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt.
Future Med Chem. 2023 Jul;15(14):1233-1250. doi: 10.4155/fmc-2023-0089. Epub 2023 Jul 19.
VEGFR-2 is one of the most effective targets in cancer treatment. The design and semi-synthesis of new theobromine derivatives as potential VEGFR-2 inhibitors. and evaluation of the synthesized compounds. Compound demonstrated excellent antiproliferative and VEGFR-2 inhibitory effects with significant apoptotic activity. It modulated the immune response by increasing IL-2 and reducing TNF-α levels. Docking and molecular dynamics simulations revealed the compound's binding affinity with VEGFR-2. Lastly, computational absorption, distribution, metabolism, excretion and toxicity studies indicated the high potential of compound for drug development. Compound could be a promising anticancer agent targeting VEGFR-2.
VEGFR-2 是癌症治疗中最有效的靶点之一。本文设计并半合成了新型可可碱衍生物作为潜在的 VEGFR-2 抑制剂，并对合成化合物进行了评价。化合物表现出优异的抗增殖和 VEGFR-2 抑制作用，并具有显著的促凋亡活性。它通过增加 IL-2 和降低 TNF-α 水平来调节免疫反应。对接和分子动力学模拟揭示了该化合物与 VEGFR-2 的结合亲和力。最后，计算吸收、分布、代谢、排泄和毒性研究表明，化合物具有很高的药物开发潜力。化合物可能是一种有前途的针对 VEGFR-2 的抗癌药物。
