New Theobromine Derivatives Inhibiting VEGFR-2: Design, Synthesis, Antiproliferative, Docking and Molecular Dynamics Simulations
Hazem A. Mahdy, Hazem Elkady, Mohammed S. Taghour, Alaa Elwan, Mohammed A. Dahab, Mohamed A. Elkady, Elsayed G.E. Elsakka, Eslam B. Elkaeed, Bshra A. Alsfouk, Ibrahim M. Ibrahim, Ibrahim H. Eissa, Ahmed M. Metwaly
Abstract
Background: VEGFR-2 is one of the most effective targets in cancer treatment. Aim: The design and semi-synthesis of new theobromine derivatives as potential VEGFR-2 inhibitors. Methods: In vitro and in silico evaluation of the synthesized compounds. Results: Compound 5b 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 5b for drug development. Conclusion: Compound 5b could be a promising anticancer agent targeting VEGFR-2.