**3. Conclusions**

A new 1*H*-indole-derived lead compound has been designed, which keeps the characteristic VEGFR-2 prohibition features. The binding potential of the lead compound was suggested by docking experiments. Interestingly, accurate binding with the VEGFR-2 active pocket was verified through MD simulations (six studies), MM-GBSA (three studies), and DFT (three studies). Additionally, ADMET studies declared the lead compound's drug-likeness. Consequently, the designed lead compound was synthesized and tested for in vitro VEGFR-2 prohibition, cytotoxicity, and safety. Compound **7** exhibited a prohibitory effect against VEGFR-2, with an IC50 value of 25 nM (lower than that of sorafenib, 35 nM), besides a promising antiproliferative potential against MCF-7 and HCT 116 cell lines, with very low IC50 values of 12.93 and 11.52 μM, as well as high selectivity indexes of 4.32 and 7.28 μM, respectively.
