Interaction of Twenty-Seven Bicyclo Derivatives with VEGF Receptors as a Therapeutic Alternative to Treat Cancer

Several studies indicate that cancer development is associated with angiogenesis, which may be conditioned for VEGFR-1, VEGFR-2, and VEGFR-3 expression. It is noteworthy that some drugs, such as axitinib, cediranib, regorafenib, and sorafenib, have been used to treat cancer. Nevertheless, some of these drugs can induce different adverse effects, such as thrombocytopenia and leukopenia. Analyzing these data, this study aimed to evaluate whether bicyclo analogs (1-27) could couple with VEGFR-1, VEGFR-2, and VEGFR-3, utilizing 3hng, 2oh4, 4sbj proteins, axitinib, cediranib, regorafenib, and sorafenib as controls in DockingServer software. Results indicate that bicyclo derivatives could interact at different sites of the 3hng, 2oh4, and 4sbj proteins surface compared to axitinib, cediranib, regorafenib, and sorafenib. Other report suggest that the inhibition constant (Ki) related to the interaction of bicylo 1 and 5 with the 3hng protein surface was lower compared with axinib, cabozatinib, cediranib, pazonib, and regorafenib drugs. Besides, the Ki for coupling of 4, 7, 8, 10, 12, and 15-22 with 2oh4 protein surface was lower compared with cabozatinib and cediranib drugs. Finally, the results for the interaction of bicyclo-analogs 4, 6-8, 10, 12, 13, 16, 18-21, 23, 24, and 26 were lower compared with axitinib and cediranib drugs. All these data suggest that bicyclo derivatives 1, 4, 6-8, 10, 12, 13, 15-24, and 26 could be good anticancer agents by modulating the VEGFR-1, VEGFR-2, and VEGFR-3 expression.