*2.8. Molecular Docking*

The molecular models of the synthesized compounds were obtained inserting their SMILES strings in University of California, San Francisco (UCSF) Chimera 1.11.2 [22]. Energy minimization of the structures was done using Chimera default conditions with Molecular Modelling Toolkit (MMTK) and Antechamber parameters [23]. AutoDock Tools 1.5.6 [24] was employed to define the rotatable bonds and atomic charges for each ligand. Download of the crystallographic structures of the receptors EGFR (PDB ID: 4HJO) and HER2 (PDB ID:3PP0) was done through Protein Data Bank (https://www.rcsb.org/) [25]. Each receptor was prepared with AutoDock Tools, removing the co-crystalized ligand along with the molecules of water included in the model, adding hydrogens and calculating the Gasteiger charges. AutoDock 4.2 [26] was employed for the docking analysis by using a grid box of 72 × 72 × 72 Å with x = 24.5, y = 9, z = −1 as the center coordinates for EGFR and x = 17.5, y = 17.5, z = 27 for HER2, with a grid point spacing of 0.375 Å. A Lamarckian genetic algorithm was used with a population size of 150, maximum number of evaluations 2.5 × 106, maximum number of generations 27000, rate of gene mutation 0.02, and rate of crossover 0.8, generating 10 docked conformations for each analyzed compound.

### *2.9. In Silico Drug-Likeness Prediction*

To determine the pharmacokinetics and physicochemical properties related to drug-likeness of the synthesized compounds, the SwissADME web server was employed [27].

### **3. Results and Discussion**

### *3.1. Synthesis of Triphenyl Imidazole Derivatives*

The 2,4,5-trisubstituted imidazole derivatives **1**–**13** were prepared from a 1,2-diketone (benzil), ammonium acetate and the corresponding aldehydes, following the known Radziszewski reaction and the methodology proposed by Puratchikody et al. with some modifications (Scheme 1) [28], with reaction yields of 64–99%. All compounds were characterized by IR and mass spectroscopy, 1H- and 13C-NMR. In the 1H NMR spectra of compounds **1**–**13**, the corresponding signals for the aromatic protons of the rings of position four and five of the imidazole heterocycle were observed, with typical displacements between 7.19–7.69 ppm. For the aromatic system of position two, all of the protons' expected shifts were observed, as were their coupling constants. In the 13C-NMR spectra, the carbons that formed the imidazole ring were observed at shifts of 159.83–143.20 ppm for carbon two, while those of position four and five were seen at 128.54–127.64 ppm. NMR spectra of the selected derivatives can be observed in Figures S1–S13 in the Supplementary Materials.

**Scheme 1.** General reaction scheme for the synthesis of 2,4,5-triphenyl-1*H*-imidazole derivatives.
