The Assessment of Anticancer and VEGFR-2 Inhibitory Activities of a New 1H-Indole Derivative: In Silico and In Vitro Approaches

Abstract

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 −40.38 Kcal/Mol. The MM-GBSA experiments named the essential amino acids in the protein–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 μM, disclosing high selectivity indexes of 6.7 and 7.5, respectively.

Design, Synthesis, Docking, DFT, MD Simulation Studies of a New Nicotinamide-Based Derivative: In Vitro Anticancer and VEGFR-2 Inhibitory Effects

“…As shown in Table 2 , all computed reactivity parameters of the title compound are listed and the energetic characteristics, including the dipole moment (Dm) and optimization energy (TE), were also determined and listed. From Figure 11 and Table 2 , the E gap between HOMO and LUMO is calculated to be 4.415 eV, which is relatively small [ 29 ]. A compound with a small frontier orbital gap means a high polarizable and chemically reactive compound.…”

Design, synthesis, anticancer evaluation, and in silico ADMET analysis of novel thalidomide analogs as promising immunomodulatory agents

“…ADMET descriptors were determined using Discovery studio 4.0 as according to the reported method 42–45 (ESI†).…”

Design, synthesis, and biological evaluation of novel bioactive thalidomide analogs as anticancer immunomodulatory agents

“…ADMET descriptors were determined using Discovery studio 4.0 as according to the reported method 58–61 (ESI†).…”