Angiogenesis is a key factor in cancer progression, which is influenced by the expression of VEGFR-1, VEGFR-2, and VEGFR-3. Several therapeutic agents, including axitinib, regorafenib, cediranib, and sorafenib, are commonly used in treating cancer, although they can cause side effects such as thrombocytopenia and leukopenia. The current study sought to evaluate how bicyclo derivatives (1-27) interact with VEGFR-1, VEGFR-2, and VEGFR-3, using the 3hng, 2oh4, and 4sbj proteins, along with axitinib, cediranib, regorafenib, and sorafenib as controls in the DockingServer software. The results showed that the bicyclo derivatives bind to specific areas of the 3hng, 2oh4, and 4sbj proteins when compared to the reference drugs. In addition, the inhibition constants (Ki) for bicyclo compounds 1 and 5 were lower than those of axitinib, cabozatinib, cediranib, pazopanib, and regorafenib in their interaction with the 3hng protein. For the 2oh4 protein, derivatives 4, 7, 8, 10, 12, and 15-22 showed lower Ki values than cabozatinib and cediranib. Finally, the interaction of bicyclo analogs 4, 6-8, 10, 12, 13, 16, 18-21, 23, 24, and 26 with the proteins yielded lower Ki values compared to axitinib and cediranib. These findings suggest that specific bicyclo derivatives could be potential anticancer agents by regulating the expression of VEGFR-1, VEGFR-2, and VEGFR-3.
