The Assessment of Anticancer and VEGFR-2 Inhibitory Activities of a New 1H-Indole Derivative: In Silico and In Vitro Approaches
Eslam B. Elkaeed; Reda G. Yousef; Hazem Elkady; Ibraheem M. M. Gobaara; Aisha A. Alsfouk; Dalal Z. Husein; Ibrahim M. Ibrahim; Ahmed M. Metwaly; Ibrahim H. Eissa
Corresponding to the reported features of anti-VEGFR-2-approved compounds, a new 1H-indole derivative (compound 7) was designed. The inhibitory potential of the designed compound was revealed via a molecular docking study that showed the appropriate binding. Then, MD simulation (six studies) over a period of 100 ns was performed to confirm the precise binding and optimum energy. Additionally, MM-GBSA reaffirmed the perfect binding, exhibiting a total precise energy of &minus:40.38 Kcal/Mol. The MM-GBSA experiments named the essential amino acids in the protein&ndash:ligand interaction, employing the binding energy decomposition and revealing the diversity of interactions of compound 7 inside the VEGFR-2 enzyme. As compound 7 is new, DFT experiments were utilized for molecular structure optimization. Additionally, the DFT results validated the coherent interaction of compound 7 with the VEGFR-2 enzyme. A good value of drug-likeness of compound 7 was acknowledged via in silico ADMET studies. Interestingly, the experimental in vitro prohibitory potential of compound 7 was better than that of sorafenib, demonstrating an IC50 value of 25 nM. Notably, the strong inhibitory effects of compound 10 against two cancer cell lines (MCF-7 and HCT 116) were established with IC50 values of 12.93 and 11.52 &mu:M, disclosing high selectivity indexes of 6.7 and 7.5, respectively.
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